Showing papers in "Autonomic Neuroscience: Basic and Clinical in 2003"
TL;DR: The hypothesis that age-related cell loss in the small and large intestines occurs exclusively in the cholinergic subpopulation of the aged rat is supported.
Abstract: Neuron loss occurs in the myenteric plexus of the aged rat. The myenteric plexus is composed of two mutually exclusive neuronal subpopulations expressing, respectively, nitrergic and cholinergic phenotypes. The goal of the present study, therefore, was to determine if neuron loss is specific to one phenotype, or occurs in both. Ad libitum fed virgin male Fischer 344 rats of 3 and 24 months of age were used in each of two neuronal staining protocols (n=10/age/neuron stain). The stomach, duodenum, jejunum, ileum, colon, and rectum were prepared as whole mounts and processed with either NADPHd or Cuprolinic Blue to stain, respectively, the nitrergic subpopulation or the entire population of myenteric neurons. Neuron numbers and sizes were determined for each preparation. Neuron counts from 24-month-old rats were corrected for changes in tissue area resulting from growth. There was no age-related loss of NADPHd-positive neurons for any of the regions sampled, whereas significant losses of Cuprolinic Blue-labeled neurons occurred in the small and large intestines of 24-month-old rats. At the two ages, the average neuron sizes were similar in the stomach and small intestine for both stains, but neurons in the large intestine were significantly larger at 24 months. In addition, numerous swollen NADPHd-positive axons were found in the large intestine at 24 months. These findings support the hypothesis that age-related cell loss in the small and large intestines occurs exclusively in the cholinergic subpopulation. It appears, however, from the somatic hypertrophy and the presence of swollen axons that the nitrergic neurons are not completely spared from the effects of age.
162 citations
TL;DR: Relief of clinical pain after shock wave application may result from reduced CGRP expression in DRG neurons, according to changes in calcitonin gene-related peptide-immunoreactive (ir) dorsal root ganglion (DRG) neurons.
Abstract: There have been several reports on the use of extracorporeal shock waves in the treatment of pseudarthrosis, calcifying tendinitis, and tendinopathies of the elbow. However, the pathomechanism of pain relief has not been clarified. To investigate the analgesic properties of shock wave application, we analyzed changes in calcitonin gene-related peptide (CGRP)-immunoreactive (ir) dorsal root ganglion (DRG) neurons. In the nontreated group, fluorogold-labeled dorsal root ganglion neurons innervating the most middle foot pad of hind paw were distributed in the L4 and L5 dorsal root ganglia. Of these neurons, 61% were CGRP-ir. However, in the shock wave-treated group, the percentage of FG-labeled CGRP-ir DRG neurons decreased to 18%. These data show that relief of clinical pain after shock wave application may result from reduced CGRP expression in DRG neurons.
108 citations
TL;DR: In this article, the authors analyzed cardiovascular and respiratory functions while subjects were inhaling fumes of pure compound (Cedrol) which was extracted from cedar wood oil, and found that exposure to Cedrol significantly decreased HR, SBP, and DBP compared to blank air while it increased baroreceptor sensitivity.
Abstract: It is well known that odors affect behaviors and autonomic functions. Previous studies reported that some compounds in cedar wood essence induced behavioral changes including sedative effects. In the present study, we analyzed cardiovascular and respiratory functions while subjects were inhaling fumes of pure compound (Cedrol) which was extracted from cedar wood oil. Vaporized Cedrol (14.2+/-1.7 microg/l, 5 l/min) and blank air (5 l/min) were presented to healthy human subjects (n=26) via a face mask, while ECGs, heart rate (HR), systolic blood pressure (SBP), diastolic BP (DBP), and respiratory rates (RR) were monitored. Statistical analyses indicated that exposure to Cedrol significantly decreased HR, SBP, and DBP compared to blank air while it increased baroreceptor sensitivity. Furthermore, respiratory rate was reduced during exposure to Cedrol. These results, along with the previous studies reporting close relationship between respiratory and cardiovascular functions, suggest that these changes in respiratory functions were consistent with above cardiovascular alterations. Spectral analysis of HR variability indicated an increase in high frequency (HF) component (index of parasympathetic activity), and a decrease in ratio of low frequency to high frequency components (LF/HF) (index of sympathovagal balance) during Cedrol inhalation. Furthermore, Cedrol inhalation significantly decreased LF components of both SBP and DBP variability, which reflected vasomotor sympathetic activity. Taken together, these patterns of changes in the autonomic parameters indicated that Cedrol inhalation induced an increase in parasympathetic activity and a reduction in sympathetic activity, consistent with the idea of a relaxant effect of Cedrol.
100 citations
TL;DR: The results indicate that rVLM premotor sympathetic cardiovascular neurons receive convergent input from the gallbladder through the splanchnic nerve and N-J acupoints through the median nerves through an opioid mechanism.
Abstract: We have shown that electroacupuncture (EA) at the Neiguan-Jianshi (N-J) acupoints over the median nerve reduces myocardial ischemia by modulating the pressor response induced by application of bradykinin on the gallbladder. The present study was designed to investigate the neural substrate underlying the prolonged modulatory effect of EA on visceral afferent input into the rostral ventral lateral medulla (rVLM). Experiments were performed on ventilated anesthetized cats. Neuronal activity was recorded while either stimulating the splanchnic nerve or applying EA at the N-J acupoints. Thirty-three cells responsive to splanchnic nerve and median nerve stimulation were antidromically driven from the intermediolateral columns, T(2)-T(4), indicating their function as premotor sympathetic neurons. These neurons also received baroreceptor input demonstrating that they were cardiovascular sympathoexcitatory cells. Arterial pulse-triggered averaging and coherence analysis demonstrated a correlation between cardiac-related discharge activity with 2.8+/-0.3 Hz rhythms and arterial blood pressure. Stimulation (2 Hz, 1-4 mA, 0.5 ms) of the splanchnic nerve for 30 s evoked excitatory responses. These neuronal responses were reduced during and after 30-min stimulation of EA at the Neiguan-Jianshi acupoints. These splanchnic nerve-induced excitatory responses in neurons subjected to 30 min of EA were reduced by 68%. Iontophoresis of naloxone promptly reversed the EA-induced inhibitory effect by 52%. Neuronal activity in the rVLM induced by splanchnic nerve stimulation was reduced for 50 (or more) min after termination of EA in 7 of 12 rVLM neurons. Our results indicate that rVLM premotor sympathetic cardiovascular neurons receive convergent input from the gallbladder through the splanchnic nerve and N-J acupoints through the median nerves. Through an opioid mechanism, EA inhibits splanchnic nerve-induced excitatory responses of these rVLM neurons. Many of these neurons receiving convergent visceral and somatic input exhibit long-lasting inhibition by EA.
91 citations
TL;DR: Investigation of changes in ovarian blood flow in response to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats showed that low-frequency EA stimulation increases OBF as a reflex response via the ovarian sympathetic nerves, whereas high-frequencyEA stimulation decreases OBf as a passive response following systemic circulatory changes.
Abstract: The purpose of the present study was to investigate changes in ovarian blood flow (OBF) in response to electro-acupuncture (EA) stimulation at different frequencies and intensities in anaesthetized rats. Whether the ovarian sympathetic nerves were involved in OBF responses was elucidated by severance of the ovarian sympathetic nerves. In addition, how changes in the systemic circulation affected OBF was evaluated by continuously recording blood pressure. OBF was measured on the surface of the left ovary using laser Doppler flowmeter. Acupuncture needles with a diameter of 0.3 mm were inserted bilaterally into the abdominal and the hindlimb muscles and connected to an electrical stimulator. Two frequencies-2 Hz (low) and 80 Hz (high)-with three different intensities-1.5, 3, and 6 mA-were applied for 35 s. Both low- and high-frequency EA at 1.5 mA and high-frequency EA at 3 mA had no effect on OBF or mean arterial blood pressure (MAP). Low-frequency EA at 3 and 6 mA elicited significant increases in OBF. In contrast, high-frequency EA with an intensity of 6 mA evoked significant decreases in OBF, followed by decreases in MAP. After severance of the ovarian sympathetic nerves, the increases in the OBF responses to low-frequency EA at 3 and 6 mA were totally abolished, and the responses at 6 mA showed a tendency to decrease, probably because of concomitant decreases in MAP. The decreased OBF and MAP responses to high-frequency EA at 6 mA remained after the ovarian sympathectomy, and the difference in the responses before and after ovarian sympathectomy was nonsignificant. In conclusion, the present study showed that low-frequency EA stimulation increases OBF as a reflex response via the ovarian sympathetic nerves, whereas high-frequency EA stimulation decreases OBF as a passive response following systemic circulatory changes.
84 citations
TL;DR: The results suggest that many functional classes of sensory neurons innervating the lower urinary tract are likely to be targets for circulating estrogens, including many nociceptor neurons.
Abstract: We have investigated whether bladder afferent neurons are likely to be targets for circulating estrogens by mapping estrogen receptor (ER) distribution in lumbosacral dorsal root ganglia (DRG) of adult female rats. Sensory neurons innervating either the detrusor or trigone regions were identified by application of fluorescent retrograde tracer dyes to the bladder wall. Labelled neurons were classified by their immunoreactivity for either type of ER (ERα or ERβ) and further compared with subpopulations of neurons containing substance P, calcitonin gene-related peptide and vanilloid receptor (a marker of polymodal nociceptors). Both ER types were expressed in numerous sensory neurons of either upper lumbar (L1/L2) or lower lumbar/sacral (L6/S1) ganglia and there was almost complete coexpression of ERα and ERβ. ER-positive neurons were mainly small–medium size (18–25-μm diameter), indicating that they may be nociceptors and/or supply visceral targets. Most bladder-projecting neurons expressed ERs and the majority of these also expressed neuropeptides or vanilloid receptor. Afferent neurons supplying detrusor and trigone regions had similar immunohistochemical features. About a third of the bladder-projecting neurons expressed both ER and vanilloid receptor, suggesting a mechanism by which estrogens could influence bladder pain. The prevalence of different chemical classes of ER-positive bladder-projecting neurons was reflected throughout the entire population of neurons in dorsal root ganglia of these spinal levels, suggesting that neurons supplying other pelvic visceral targets may have similar chemical profiles. These results suggest that many functional classes of sensory neurons innervating the lower urinary tract are likely to be targets for circulating estrogens, including many nociceptor neurons. The coexistence of ERα and ERβ suggests a broad range of potential mechanisms by which estrogens may exert their genomic effects in this system.
74 citations
TL;DR: In this article, the authors investigated whether the two main divisions of the autonomic nervous system, the sympathetic and parasympathetic systems, may support different types of exchange with the external environment.
Abstract: In light of the nonequilibrium thermodynamics by I. Prigogine, the autonomic nervous system as a whole may be viewed as a dissipative structure progressively assembled in the course of evolution, plastically and rhythmically interfaced between forebrain, internal and external environments, to regulate energy, matter and information exchanges. In the present paper, this hypothesis is further pursued to verify whether the two main divisions of the autonomic nervous system, the sympathetic and parasympathetic systems, may support different types of exchange with the external environment. Previous data from hypothalamic stimulation experiments, studies of locus coeruleus function and available data on behavioral functional organization indicate that (1) tight engagement with the external environment, (2) high level of energy mobilization and utilization and (3) information mainly related to exteroceptive sensory stimulation characterize a behavioral prevalence of sympathoadrenal activation. On the other hand, (1) disengagement from the external environment, (2) low levels of internal energy and (3) dominance of proprioceptive information characterize a behavioral prevalence of vagal tone. Behavioral matter exchanges such as feeding, drinking, micturition and defecation are equally absent at the extreme of sympathoadrenal and vagally driven behaviors. The autonomic nervous system as a whole is genetically determined, but the sympathoadrenal system has been mainly designed to organize the visceral apparatus for an action to be performed by the biological system in the external environment and to deal with the novelty of task and of the environment, while the functional role of the parasympathetic is to prepare the visceral apparatus for an action to be performed by the biological system on itself, for recovery and self-protection (homeostasis), and is reinforced by repetition of phylo- and ontogenetically determined patterns. The available clinical data further support this interpretation indicating that an increased sympathetic and a decreased vagal tone may represent a consistent risk factor for cardiovascular diseases.
71 citations
TL;DR: The two groups of diabetic rats and diabetic rats treated with ascorbic acid showed reduction in the number and an increased area of the myosin-V-immunostained myenteric neurons and increased relative proportion of NADPH-d-stained neurons in diabetic rat groups, however, the area of these neurons in the diabetic rats group was larger than those evidenced in the nondiabetic rat group.
Abstract: We investigated the effect of the ascorbic acid on the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-stained and myosin-V myenteric neurons in the ileum of chronically diabetic rats The study was performed 4 months after inducing experimental diabetes with streptozotocin Diabetic rats showed increased (p<005) glycaemia and glycated haemoglobin Three groups were compared, ie, nondiabetic rats, diabetic rats and diabetic rats treated with ascorbic acid Myosin-V immunohistochemistry and NADPH-d histochemistry were employed We investigated the areas of 500 cell bodies of myosin-V neurons and of 500 NADPH-d-stained neurons from all groups The quantitative analysis was performed by using an area of 896 mm(2) from each ileum The two groups of diabetic rats and diabetic rats treated with ascorbic acid showed reduction in the number and an increased area of the myosin-V-immunostained myenteric neurons In addition, we observed increased relative proportion of NADPH-d-stained neurons in diabetic rats and diabetic rats treated with ascorbic acid However, the area of these neurons in the diabetic rats group was larger than those evidenced in the nondiabetic rats and diabetic rats treated with ascorbic acid
68 citations
TL;DR: The results were consistent with an increased parasympathetic activity and a reduced sympathetic activity of pupillary light reflex in endurance-trained runners, supporting the hypothesis of a generalized "dysautonomy" associated with this type of training.
Abstract: Spectral analysis of heart rate variability has become a noninvasive standard method for assessment of autonomic nervous system activity in athletes. The effect of exercise training on autonomic regulation of pupillary light reflex is not known. The purpose of this study was to evaluate pupil autonomic function in athletes. We studied 46 highly trained athletes practicing gymnastics, swimming, long-distance running, soccer, and 51 healthy control subjects, using a portable infrared pupillometry. Five left pupil light response curves were recorded for each subject; the 485 pupillogram records were processed by a computer system. The following pupillometric parameters calculated were significantly higher (P<0.05) in runners than in controls: reflex amplitude (2.1 mm; 95% CI, 1.9-2.3 vs. 1.8 mm; 95% CI, 1.7-1.9), mean percent reflex amplitude of initial diameter (34%; 95% CI, 32-37 vs. 30%, 95% CI, 28-31) and mean time at which pupil redilated 75% of reflex amplitude (2.15 s; 95% CI, 1.99-2.31 vs. 1.86 s; 95% CI, 1.78-1.93). Sex, age, height, weight, body mass index and years of sports practice had no significant influence in the evaluated parameters. The results were consistent with an increased parasympathetic activity and a reduced sympathetic activity of pupillary light reflex in endurance-trained runners, supporting the hypothesis of a generalized "dysautonomy" associated with this type of training.
66 citations
TL;DR: It is demonstrated that the paraventricular nucleus plays a critical role in the regulation of renal SND even under basal conditions in anesthetized animals.
Abstract: Activity of the hypothalamic paraventricular nucleus (PVN) is essential for the maintenance of vasomotor sympathetic nerve discharge (SND) and blood pressure even in the anesthetized rat. Inactivation of the paraventricular nucleus results in a large depressor and sympathoinhibitory response. The current study was designed to examine the regulation of renal sympathetic nerve activity by the paraventricular nucleus in both hypertensive and normotensive rats. Experiments were performed in anesthetized, artificially ventilated spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Renal sympathetic nerve activity, blood pressure and heart rate were recorded. Bilateral microinjections of the GABA(A) receptor agonist, muscimol (1 nmol in 100 nl), were made into the paraventricular nucleus. Decreases in blood pressure (SHR: from 111+/-3 to 54+/-4 mm Hg; WKY: 84+/-2 to 48+/-3 mm Hg), heart rate (SHR: 336+/-8 to 289+/-12 bpm; WKY 309+/-7 to 258+/-13 bpm) and renal sympathetic nerve activity (to 46+/-11% and 33+/-7% of control in the WKY and SHR, respectively) were observed. The renal nerve response to inactivation of the paraventricular nucleus was not different between the strains, indicating that modulation of renal sympathetic nerve activity by the paraventricular nucleus is similar in these rat strains. This is different from the previously reported effect of paraventricular nucleus inhibition on lumbar sympathetic nerve activity [Hypertension 39 (2002) 275]. Overall, we demonstrate that the paraventricular nucleus plays a critical role in the regulation of renal SND even under basal conditions in anesthetized animals.
56 citations
TL;DR: It is suggested that long-term VNS might slightly affect cardiac autonomic function with a reduction of the HF component of the spectrum during night and a flattening of sympathovagal circadian changes, not inducing, however, clinically relevant cardiac side effects.
Abstract: Vagus nerve stimulation (VNS) has been suggested as an adjunctive treatment for drug-resistant epilepsy when surgery is inadvisable. The overall safety profile of VNS seems to be favorable as only minor adverse effects have been described. The purpose of this study was to determine if cardiac vagal tone is eventually modified by short- and long-term VNS. The effects of short- and long-term VNS were evaluated in seven subjects with intractable epilepsy. Autonomic cardiac function has been carried out by means of a 24-h analysis of RR variability at baseline ( t 0 ), 1 month ( t 1 , short-term VNS) and 36 months after VNS initiation ( t 2 , long-term VNS). Frequency- and time-domain parameters were calculated. Periodic cardiological and neurological evaluations were performed. Clinically relevant cardiac effects were not observed throughout the study. Despite the limited number of patients and the variety of data among them, for all the patients, a common trend towards a nocturnal decrease in the high-frequency (HF) component of the spectrum was observed after long-term VNS (mean±S.D.: 40±18 normalized units (nu) at t 0 , 38±17 nu at t 1 , 18±10 nu at t 2 ; p t 2 vs. either t 0 or t 1 ). The day-to-night changes in the power of low-frequency (LF) and HF components were significantly blunted after long-term VNS (LF day-to-night change: +16±13 nu at t 0 and +15±8 nu at t 1 vs. +3±13 nu at t 2 , p t 0 and −13±11 nu at t 1 vs. +3±12 nu at t 2 , p Throughout the neurological follow-up, one subject became seizure-free, three experienced a seizure reduction of >50%, two patients of Our findings suggest that long-term VNS might slightly affect cardiac autonomic function with a reduction of the HF component of the spectrum during night and a flattening of sympathovagal circadian changes, not inducing, however, clinically relevant cardiac side effects.
TL;DR: It appears that increased NGF levels that may be noted after sympathectomy are capable of producing some aspects of vascular remodeling via different signaling cascades in choroidal endothelial cells in culture.
Abstract: We have previously shown that sympathetic denervation results in significant blood vessel growth of the choroid and retina. The mechanism of this growth remains unclear. Since sympathetic denervation can result in increased nerve growth factor (NGF) levels, it was the goal of this study to determine if choroidal and retinal endothelial cells in culture would respond to nerve growth factor and if nerve growth factor promote endothelial cell migration and proliferation, two components of angiogenesis. Western blotting with phospho-specific antibodies, cell migration, and cell proliferation assays were employed to determine NGF effects on both choroidal and retinal cell growth. NGF treatment produced phosphorylation of TrkA in choroidal and retinal endothelial cells. NGF stimulation resulted in activation of ERK1/2, Akt, and Src in choroidal endothelial cells, while little phosphorylation was noted following NGF treatment in retinal endothelial cells. NGF increased choroidal endothelial cell migration by 50% over control and this was inhibited by pretreatment with LY294002 (PI3K inhibitor), Akt inhibitor, and MMP2/9 inhibitor. KT5823, PD98059, and PP2 did not affect choroidal cell migration. NGF also produced a 47% increase in choroidal endothelial cell proliferation, which was blocked by PP2, LY294002, Akt inhibitor, KT5823, and PD98059. NGF stimulation did not alter retinal endothelial cell migration or proliferation. Thus, it appears that increased NGF levels that may be noted after sympathectomy are capable of producing some aspects of vascular remodeling via different signaling cascades in choroidal endothelial cells in culture.
TL;DR: The data suggest that cholinergic pathways modulate the acute colonic inflammatory response associated with the dinitrobenzene sulfonic acid model, with central pathways exerting a greater protective effect relative to peripheral pathways.
Abstract: Recent studies have suggested that neuroimmune interactions modulate intestinal mucosal immune responses. In the current study, we examined the role of cholinergic pathways in modulating the severity of acute dinitrobenzene sulfonic acid colitis, using pharmacological agents to suppress acetylcholinesterase in Sprague–Dawley rats, and evaluating the colitis in the cholinergic hyperresponsive Flinder's sensitive line rats and their control counterparts, the Flinder's resistant line. Colitis was induced by intrarectal dinitrobenzene sulfonic acid (80 mg ml −1 in 50% ethanol); controls received intrarectal saline. Sprague–Dawley rats received an acetylcholinesterase inhibitor, physostigmine (50 μg kg −1 s.c.) or neostigmine (50 μg kg −1 s.c.), 30 min prior to intrarectal dinitrobenzene sulfonic acid; controls received saline vehicle. On day 5, the macroscopic damage score, myeloperoxidase activity (an estimate of granulocyte infiltration) and smooth muscle thickness were evaluated in the inflamed colonic segment. Significant increases in macroscopic damage score and colonic smooth muscle thickness were observed in Sprague–Dawley and Flinder's Resistant Line rats on day 5 following intrarectal dinitrobenzene sulfonic acid compared to saline controls. Increased myeloperoxidase activity was also observed in dinitrobenzene sulfonic acid-treated Sprague–Dawley rats and Flinder's Resistant Line rats. In contrast, Flinder's Sensitive Line rats failed to demonstrate a significant rise in macroscopic damage, smooth muscle layer thickness, or myeloperoxidase activity on day 5 following intrarectal dinitrobenzene sulfonic acid when compared to saline-treated Flinder's Sensitive Line controls. Neostigmine and physostigmine treatment prior to intrarectal dinitrobenzene sulfonic acid significantly attenuated macroscopic damage score, myeloperoxidase activity and smooth muscle thickness on day 5 compared to colitic Sprague–Dawley controls. Significantly greater reductions in myeloperoxidase activity were observed with physostigmine vs. neostigmine pretreatment. These data suggest that cholinergic pathways modulate the acute colonic inflammatory response associated with the dinitrobenzene sulfonic acid model, with central pathways exerting a greater protective effect relative to peripheral pathways. Further studies are required to determine the contributions of sites in the nervous system and neuro-effector junctions.
TL;DR: DAN is a significant independent risk factor for the occurrence of stroke in type 2 diabetic patients, and may occur due to accelerated cerebral vascular damage and alterations in the regulation of cerebral blood flow in diabetic patients with DAN.
Abstract: Objective : To ascertain risk factors associated with the occurrence of strokes in type 2 diabetes over a 5-year follow-up period. Background : Diabetic patients are at increased risk for cardiovascular disease when compared to non-diabetic patients. Strokes are a significant source of morbidity and mortality. Design/Methods : We evaluated the relationship between a number cardiovascular risk factors in 950 normotensive and hypertensive type 2 diabetic patients enrolled in the Appropriate Blood Pressure Control in Diabetes (ABCD) trial on the incidence of stroke. We analyzed data from this longitudinal study to evaluate the relationships between various baseline risk factors and the occurrence of strokes. Results : A number of baseline risk factors were associated with the occurrence of strokes including history of a stroke ( p =0.02) and heart failure ( p =0.004) at baseline, age ( p =0.004), longer duration of diabetes ( p =0.03), higher systolic blood pressure ( p =0.005), an abnormal ankle/brachial index ( p =0.05), decreased duration on the exercise treadmill test at baseline ( p =0.009), the presence of retinopathy ( p =0.02), overt albuminuria ( p =0.03) and the presence of diabetic autonomic neuropathy (DAN) as defined as a borderline or abnormal E/I ratio ( p =0.016). Other variables that were tested but were not significantly associated included gender, duration of hypertension, diastolic blood pressure and smoking. When applying a multiple logistic regression model, DAN (OR=2.2, 95% CI=1.10–4.44), along with a history of heart failure (OR=7.4, 95% CI=2.12–26.15) and strokes (OR=3.4, 95% CI=1.02–11.00) at baseline were each associated with the occurrence of strokes. Conclusions : In the present study of type 2 diabetic patients, DAN is a significant independent risk factor for the occurrence of stroke. This may occur due to accelerated cerebral vascular damage and alterations in the regulation of cerebral blood flow in diabetic patients with DAN.
TL;DR: Data indicate that, in DOCA-salt hypertension, there is an increased norepinephrine release from sympathetic nerves associated with mesenteric arteries and veins, which results in an increase in the amplitude of neurogenic constrictions.
Abstract: Sympathetic control of arteries and veins may be altered in hypertension. To test this hypothesis, constrictions of mesenteric arteries and veins caused by nerve stimulation and by norepinephrine (NE) and ATP were studied in vitro in tissues from deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rats. In DOCA-salt arteries, the maximum neurogenic response was greater than that in sham arteries. The P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS, 10 μM), greatly reduced neurogenic responses in sham but not DOCA-salt arteries. The α1-adrenergic receptor antagonist, prazosin (0.1 μM), inhibited responses in DOCA-salt but not sham arteries. Concentration–response curves for norepinephrine and ATP were similar in sham and DOCA-salt arteries, indicating that reactivity to sympathetic vasoconstrictor transmitters was not changed in DOCA-salt arteries. Neurogenic constrictions in sham and DOCA-salt veins were similar in amplitude, and they were completely blocked by prazosin. However, concentration–response curves for norepinephrine in DOCA-salt veins were right-shifted compared to those in sham veins. Cocaine (10 μM) and corticosterone (10 μM) caused a leftward shift in norepinephrine concentration–response curves in DOCA-salt but not sham veins. Norepinephrine content was decreased in DOCA-salt arteries and veins, and there was an increased norepinephrine transporter (NET) level in DOCA-salt veins. These data indicate that, in DOCA-salt hypertension, there is an increased norepinephrine release from sympathetic nerves associated with mesenteric arteries and veins. In arteries, this results in an increase in the amplitude of neurogenic constrictions. In veins, increased norepinephrine release maintains neurogenic constrictions in the presence of increased NET levels.
TL;DR: The suppressive effect of SCS on colonic sensitivity suggests that SCS may have therapeutic potential for the treatment of visceral pain of gastrointestinal origin associated with abdominal cramping and painful abdominal spasms.
Abstract: The mechanisms underlying the cause and treatment of visceral pain of gastrointestinal origin are poorly understood. Previous clinical studies have shown that spinal cord stimulation (SCS) attenuates neuropathic and ischemic pain, and animal experiments have provided knowledge about probable physiological mechanisms. The goal of the present study was to investigate whether SCS influences colonic sensitivity in a conscious rat. A visceromotor behavioral response (VMR), induced by colorectal distention, was used to quantify the level of colonic sensitivity. Under anesthesia, an electrode (cathode) was placed on the dorsal surface of the spinal cord at L1. One week after implantation of the SCS electrode, the effects of stimulation delivered with different intensities (50 Hz, 0.2 ms for 30 min) on colonic sensitivity were determined. Nociceptive levels of colorectal distention (60 mm Hg for 10 min) induced an enhanced VMR quantified as an increased number of abdominal muscle contractions compared to controls in which the balloon catheter was inserted into the colorectal region but not distended. Colonic sensitization with acetic acid increased the VMR to innocuous levels of colorectal distention (30 mm Hg for 10 min). We found that SCS induced a significant depression of the VMR produced by colorectal distention in both normal rats and those with sensitized colons. The suppressive effect of SCS on colonic sensitivity suggests that SCS may have therapeutic potential for the treatment of visceral pain of gastrointestinal origin associated with abdominal cramping and painful abdominal spasms.
TL;DR: The induced expression of VIP in cultured adult myenteric neurons indicates that VIP is important for neuronal adaptation, maintenance and survival.
Abstract: Adult neurons possess the ability to adapt to a changing environment. Loss of target-derived neurotrophic factors due to axotomy or isolation by culturing is known to induce changes in neuropeptide expression in several types of peripheral neurons. The aim of the present study was to investigate changes in the expression of vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS) in cultured myenteric ganglia and dissociated neurons. Myenteric ganglia and neurons from rat small intestine were dissociated and cultured for up to 21 days. Immunocytochemistry was used to determine the total number of neurons and the proportions of subpopulations containing VIP or NOS or both in preparations of whole mounts (controls used to determine the conditions in vivo), myenteric ganglion culture and dissociated myenteric neuronal culture. In situ hybridization was used to determine changes in the expressions of NOS and VIP mRNA. The relative number of VIP-expressing neurons increased significantly during culturing. The percentage of all neurons expressing VIP was 3.6±0.3% in whole mounts, 22–24% in cultured myenteric ganglia, and up to 35% in cultured dissociated neurons. NOS-expressing neurons constituted approximately 30–40% of all neurons in whole mounts as well as in cultured ganglia or dissociated neurons. A dramatic increase in NOS/VIP-containing neurons were detected in cultured neurons irrespective of whether they were arranged in ganglia or dissociated, as compared to whole mount preparations. This suggests that the NOS-containing neurons are the ones that increase their VIP expression. The induced expression of VIP in cultured adult myenteric neurons indicates that VIP is important for neuronal adaptation, maintenance and survival.
TL;DR: The results of experiment 1 showed that lesioned animals consume significantly larger amounts of food and water compared with controls at 6, 12, and 24 h (but not at 48 or 72 h) after the surgical intervention, and experiment 2 revealed a greater intake of liquid food by capsaicin-treated animals at the first post-surgical sessions.
Abstract: The vagus nerve has been related to the short-term control of food intake. This involvement has previously been explored by examining the food intake of animals after recovery from a vagotomy or immediately after the intervention, among other methods. In the present work, a study was conducted on the impact of the perivagal application of capsaicin (a specific neurotoxic treatment that destroys most of the vagal afferent pathways) on the intake of water and solid (experiment 1) or liquid (experiment 2) food presented after the surgery The results of experiment 1 showed that lesioned animals consume significantly larger amounts of food and water compared with controls at 6, 12, and 24 h (but not at 48 or 72 h) after the surgical intervention. Likewise, experiment 2 revealed a greater intake of liquid food by capsaicin-treated animals at the first post-surgical sessions. These data are discussed in terms of the role played by vagal afferent fibers in the control of short-term food intake.
TL;DR: Both parasympathetic vagal cardiac nerves and sympathetic cardiac nerves are activated during the nasopharyngeal reflex, with increased vagal effects in the sino-atrial node, and increased sympathetic effects inThe ventricular myocardium.
Abstract: Electrocardiographic responses were assessed in conscious rabbits when the nasopharyngeal reflex was elicited by inhalation of formaldehyde vapour. There was a profound fall in heart rate (224±5 to 64±4 beats per min (bpm)) associated with abnormal or absent P-waves. There were no changes in the QRS complex. The R–T interval (control value 118±4 ms) was initially shortened to 107±3 ms and then prolonged to 130±4 ms. Heart rate and P-wave changes were prevented by muscarinic cholinergic blockade with methylscopolamine. The R–T shortening was reduced by 79±4% by β-adrenergic blockade with propranolol. Methylscopolamine also unmasked small tachycardic responses (5–25 bpm) in 5/7 animals. This tachycardia was prevented by propranolol. Thus both parasympathetic vagal cardiac nerves and sympathetic cardiac nerves are activated during the nasopharyngeal reflex, with increased vagal effects in the sino-atrial node, and increased sympathetic effects in the ventricular myocardium.
TL;DR: The results suggest that distention activates vagal afferents in the gastrointestinal tract and the inhibitory neurotransmitter suppresses the activity of the dorsal motor nucleus of the vagus neurons.
Abstract: Vago-vagal reflexes play an integral role in the regulation of gastrointestinal function. Although there have been a number of reports describing the effects of various stimuli on the firing rates of vagal afferent fibers and vagal motor neurons, little is known regarding the neurotransmitters that mediate the vago-vagal reflexes. In the present work, we investigated the role of glutamate in the vago-vagal reflex induced by gastrointestinal distention. Using single-cell recording techniques, we determined the effects of gastric and duodenal distention on the firing rates of gut-related neurons in the dorsal vagal complex, in the absence and presence of glutamate antagonists. Kynurenic acid, a competitive glutamate receptor antagonist, injected into the dorsal vagal complex, blocked the neuronal response of neurons in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract to gastrointestinal distention. Injection of glutamate into the nucleus of the solitary tract produced inhibition of dorsal motor nucleus of the vagus neurons that were also inhibited by gastric and/or duodenal distention. Thus, the distention-induced inhibition of dorsal motor nucleus of the vagus neurons may be mediated by glutamate-induced excitation of gut-related nucleus of the solitary tract neurons. To investigate the role of the various glutamate receptor subtypes in the distention-induced events, we studied the effects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist, and DL-2-amino-5-phosphonopentanoic acid (DL-AP5), a selective NMDA receptor antagonist. CNQX injected into the dorsal vagal complex either blocked or attenuated the inhibitory response of the neurons in the dorsal motor nucleus of the vagus and nucleus of the solitary tract neurons to gastric and duodenal distention. In contrast, DL-AP5 had less effect, especially in the vago-vagal reflex elicited by gastric distention. The results suggest (1) distention activates vagal afferents in the gastrointestinal tract; (2) the central branches of the vagal afferents from the gut terminate in the nucleus of the solitary tract and release glutamate that mainly act on non-NMDA receptors; (3) glutamate activates the inhibitory neurons in the nucleus of the solitary tract that project to the dorsal motor nucleus of the vagus; and (4) the inhibitory neurotransmitter suppresses the activity of the dorsal motor nucleus of the vagus neurons. For the excitatory neuronal responses of the dorsal motor nucleus of the vagus neurons to gastrointestinal distention, the possible circuit is that the vagal afferents containing glutamate directly activate the receptors on the dendrites of the dorsal motor nucleus of the vagus.
TL;DR: The results indicate that there are four kinds of neurons among the CVN: non-cholinergic CVN in the AmE, cholinergic and CGRP-containing CVNIn the AmC, AmS and AmL, and Cholinergic or cholin neurotransmitter-related peptide and NOS- containing CVn in the DMV.
Abstract: Cardiac vagal preganglionic neurons (CVN) control cardiac activity by negative chronotropic, dromotropic and inotropic effects. We attempted to characterize the distribution and neuronal properties of the CVN by using double labeling with the retrograde tracer cholera toxin B subunit (CTb) and immunohistochemistry for choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP) or nitric oxide synthase (NOS). Injection of CTb into the sinoatrial ganglia resulted in many retrogradely labeled of neurons in the dorsal motor nucleus of the vagus (DMV), the compact (AmC), semicompact (AmS), loose (AmL), external (AmE) formations of the nucleus ambiguus, and the intermediate zone (IZ) between DMV and the nucleus ambiguus. Almost all CTb-labeled neurons showed ChAT immunoreactivity in the DMV, AmC, AmS, AmL and IZ, but most of the CTb-labeled neurons showed no ChAT immunoreactivity in the AmE. Most of the CTb-labeled neurons were double-labeled with CGRP immunoreactivity in the AmC, AmS and AmL, but a few double-labeled neurons were found in the DMV, IZ and AmE. A few CTb-labeled neurons were double-labeled with NOS immunoreactivity only in the DMV. No TH-immunoreactive neurons were found among the CVN. These results indicate that there are four kinds of neurons among the CVN: non-cholinergic CVN in the AmE, cholinergic and CGRP-containing CVN in the AmC, AmS and AmL, and cholinergic or cholinergic and NOS-containing CVN in the DMV.
TL;DR: It is found that SEFs and LF/ HF or LF decreased simultaneously and periodically, suggesting simultaneous depression of EEG activity and relative sympathetic activity, and SEFs significantly correlated with LF/HF and LF in all subjects during sleep, but not with HF.
Abstract: We investigated the relationship between electroencephalogram (EEG) activity and autonomic nervous system function using spectral analyses of EEG and heart rate variability (HRV) in healthy subjects during sleep. Eleven subjects were enrolled in this study. From EEG, the spectral edge frequencies (SEFs including SEF50, SEF90 and SEF95) were calculated. From electrocardiogram (ECG), the spectral powers of low-frequency band (LF: 0.04-0.15 Hz), high-frequency band (HF: 0.15-0.4 Hz) and the ratio of LF to HF (LF/HF) were calculated. During sleep, each set of data was obtained as the average of a 5-min measurement. We found that SEFs and LF/HF or LF decreased simultaneously and periodically, suggesting simultaneous depression of EEG activity and relative sympathetic activity, and SEFs significantly correlated with LF/HF and LF in all subjects during sleep, but not with HF. The existence of a clear correlation of SEFs with LF or LF/HF may offer a simple approach to estimate the relationship between EEG activity and autonomic nervous system function during sleep.
TL;DR: The results suggest that the increase in Hpc CBF during walking is independent of MAP and attributable at least to activation of the nAChRs by the cholinergic vasodilator nerves projecting to the hippocampus and to production of NO in the hippocampus.
Abstract: Recent studies in our laboratory have demonstrated that stimulation of the septal complex (i.e., the medial septal nucleus and the nucleus of the diagonal band) increases extracellular acetylcholine (ACh) release and, consequently, results in an increase in regional cerebral blood flow in the hippocampus (Hpc CBF) via activation of the nicotinic ACh receptors (nAChRs) [Neurosci. Lett. 107 (1989) 135; Neurosci. Lett. 112 (1990a) 263]. The present study aimed to examine the effects of walking on Hpc CBF, measured by laser Doppler flowmetry, in conscious rats. Walking at a moderate speed (4 cm/s) on a treadmill for 30 s produced increases in Hpc CBF and mean arterial pressure (MAP), reaching 107 +/- 1% and 105 +/- 1% of the prewalking control values, respectively. Walking for 3 min produced an increase in ACh release in the extracellular space of the hippocampus. The increase in Hpc CBF during walking was attenuated by mecamylamine (abbreviated as MEC here; 2 mg/kg, i.v.), a nAChR antagonist permeable to the blood-brain barrier (BBB), but not by hexamethonium (denoted as C6 here; 20 mg/kg, i.v.), a nAChR antagonist impermeable to the BBB, while the walking-induced increase in MAP was abolished by either agent. The response of Hpc CBF and MAP were not altered by atropine (abbreviated as ATR here; 0.5 mg/kg, i.v.), a muscarinic AChR antagonist permeable to the BBB. The increase in Hpc CBF during walking was attenuated by N(omega)-nitro-L-arginine methyl ester (L-NAME, 3 and 30 mg/kg, i.v.), a nitric oxide synthase (NOS) inhibitor, and the reduced responses were reversed following the intravenous (i.v.) administration of a physiological precursor of NO, L-arginine (600 mg/kg). The results suggest that the increase in Hpc CBF during walking is independent of MAP and attributable at least to activation of the nAChRs by the cholinergic vasodilator nerves projecting to the hippocampus and to production of NO in the hippocampus.
TL;DR: It is concluded that Dogiel type II neurons are all AH neurons and are probably intrinsic sensory neurons that could be involved in long-term changes in excitability in the colon.
Abstract: Well-defined correlations between morphology, electrophysiological properties and the types of synaptic inputs received are established for myenteric neurons in the guinea pig ileum. However, in the distal colon, the correlations between AH electrophysiological properties, presence of fast excitatory post-synaptic potentials (EPSPs) and neuronal shape have been inadequately resolved and it is unknown whether any colon neurons receive synaptic inputs that generate sustained excitation. In this work, we have used intracellular recording, dye filling via the recording electrode, and immunohistochemistry to classify distal colon neurons. Neurons (24 of 168) had Dogiel type II morphology and 42% of these were dendritic type II neurons, compared to about 10% in the ileum. All Dogiel type II neurons had AH electrophysiological properties, including a prolonged post-spike after-hyperpolarization (AHP). None of these received fast excitatory post-synaptic potentials, 11 of 22 tested exhibited sustained slow post-synaptic excitation (SSPE) in response to 1 Hz pre-synaptic stimulation and 13 of 15 tested were immunoreactive for calbindin. Neurons (127) had Dogiel type I, filamentous or other uniaxonal cell shape and S type electrophysiology. Neurons of this group had fast excitatory post-synaptic responses to stimulation of synaptic inputs, but did not exhibit a prolonged post-spike after-hyperpolarization or sustained slow post-synaptic excitation. Another group of neurons (17) had both AH electrophysiological characteristics and fast excitatory post-synaptic potentials. These neurons had Dogiel type I, filamentous or other uniaxonal shapes, but none had Dogiel type II morphology and none showed sustained slow post-synaptic excitation. It is concluded that Dogiel type II neurons are all AH neurons and are probably intrinsic sensory neurons that could be involved in long-term changes in excitability in the colon. All other neurons are monoaxonal; these are motor neurons and interneurons, and most are S neurons, electrophysiologically. A small number of monoaxonal neurons display AH electrophysiology and also receive fast excitatory synaptic inputs. These include motor and interneurons, but not sensory neurons.
TL;DR: A major finding is the connection between the ventral caudal raphe and the nucleus of the solitary tract, which could participate in chemoreception and central regulation of cardiorespiratory reflexes during human perinatal development; it is, therefore, relevant to the study of sudden infant death syndrome (SIDS).
Abstract: The nucleus of the solitary tract (nTS) is a major site of brainstem control of vital functions (e.g., cardiovascular reflexes and respiration). We examined anatomic relationships of the human nucleus of the solitary tract, using a bidirectional lipophilic fluorescent tracer 1-1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in 10 postmortem human fetal midgestational medullae oblongatae. Labeling by diffusion of DiI from the nucleus of the solitary tract included: (1) neuropil of all future subdivisions of the nucleus of the solitary tract ipsilateral to the DiI crystal; (2) stellate cells in the caudal raphe at the junction of the nucleus raphe pallidus and the arcuate nucleus at the ventral medullary surface, as well as single fibers along the caudal raphe and the arcuate nucleus; (3) cells and fibers in other medullary areas related to autonomic and respiratory control, including the dorsal motor nucleus of the vagus, nucleus ambiguus complex/ventral respiratory group, rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM), and medullary reticular formation. The pattern of connections of the nucleus of the solitary tract already established by midgestation in the human fetus is consistent with the pattern previously demonstrated in adult experimental animals. A major finding of the study is that of the stellate cells at the junction of nucleus raphe pallidus and the arcuate nucleus at the ventral medullary surface, which project to the nucleus of the solitary tract, and could be homologous to chemosensitive serotonergic neurons at the midline ventral medullary surface of experimental animals. This connection between the ventral caudal raphe and the nucleus of the solitary tract may participate in chemoreception and central regulation of cardiorespiratory reflexes during human perinatal development; it is, therefore, relevant to the study of sudden infant death syndrome (SIDS).
TL;DR: The data suggest that diabetes-induced oxidative stress plays a role in diabetes- induced baroreceptor dysfunction and that the alpha-lipoic acid may have a beneficial effect in treatment of diabetic autonomic neuropathy.
Abstract: Autonomic neuropathies, common complications of prolonged diabetes, may result from diabetes-induced increased oxidative stress. Recently, we found that the afferent component of the baroreceptor reflex is attenuated in streptozotocin-induced diabetic rats. This study sought to determine the influence of the anti-oxidant, α-lipoic acid on the diabetes-induced deficits of the afferent limb of the baroreceptor reflex and on plasma malondialdehyde (a measure of lipid peroxidation). The number of c-Fos-ir neurons in the nucleus tractus solitarius in response to phenylephrine-induced baroreceptor activation was used as an index of the integrity of the afferent limb of the baroreceptor reflex. Groups of streptozotocin-induced diabetic and non-diabetic control rats, maintained from 8 to 16 weeks, were treated with α-lipoic acid (100 mg kg−1 IP, 5×/week), or vehicle for the last 4 weeks prior to the experimental procedure. Vehicle-treated diabetic rats had elevated plasma malondialdehyde levels when compared to non-diabetic rats. α-Lipoic acid-treated diabetic rats had plasma malondialdehyde levels similar to those seen in non-diabetic rats and less than those of vehicle-treated diabetic rats at both the 8- and 16-week time points. α-Lipoic acid treatment did not affect the baseline (absence of baroreceptor activation) presence of c-Fos-ir in the nucleus tractus solitarius. In response to phenylephrine and regardless of treatment, the diabetic and control rats displayed increases in blood pressure and reflex bradycardia. As previously reported, phenylephrine-induced baroreceptor activation resulted in significantly fewer c-Fos-ir neurons in the nucleus tractus solitarius (commissural and caudal subpostremal regions) of diabetic rats when compared to non-diabetic rats at both 8- and 16-week time points. Four weeks of α-lipoic acid treatment reversed the diabetes-induced decrement in the numbers of c-Fos-ir neurons in the nucleus tractus solitarius in response to baroreceptor activation. α-Lipoic acid-treated diabetic rats showed the same phenylephrine-induced c-Fos response in the nucleus tractus solitarius as those of α-lipoic-acid- and vehicle-treated control rats at both 8- and 16-week time points. These data suggest that diabetes-induced oxidative stress plays a role in diabetes-induced baroreceptor dysfunction and that the α-lipoic acid may have a beneficial effect in treatment of diabetic autonomic neuropathy.
TL;DR: It is suggested that the ELF-MF to which humans are exposed in their daily lives has no acute influence on the activity of the cardiovascular autonomic nervous system (ANS) that modulates the heart rate.
Abstract: This study is a reexamination of the possibility that exposure to extremely low frequency alternating magnetic field (ELF-MF) may influence heart rate (HR) or its variability (HRV) in humans. In a wooden room (cube with 2.7-m sides) surrounded with wire, three series of experiments were performed on 50 healthy volunteers, who were exposed to MFs at frequencies ranging from 50 to 1000 Hz and with flux densities ranging from 20 to 100 μT for periods ranging from 2 min to 12 h. In each experiment, six indices of HR/HRV were calculated from the RR intervals (RRIs): average RRI, standard deviation of RRIs, power spectral components in three frequency ranges (pVLF, pLF and pHF), and the ratio of pLF to pHF. Statistical analyses of results revealed no significant effect of ELF-MFs in any of the experiments, and suggested that the ELF-MF to which humans are exposed in their daily lives has no acute influence on the activity of the cardiovascular autonomic nervous system (ANS) that modulates the heart rate.
TL;DR: In this paper, the expression of tyrosine hydroxylase (TH) and the norepinephrine transporter (NET), measured using Western analysis, are changed during pregnancy and the estrous cycle.
Abstract: In females, sympathetic activity varies with changes in reproductive status, but whether expression of proteins critical to the function of sympathetic neurons is also altered is unknown. Therefore, the present study tested the hypothesis that, in rat adrenal gland and superior cervical ganglia, the expression of tyrosine hydroxylase (TH) and the norepinephrine transporter (NET), measured using Western analysis, are changed during pregnancy and the estrous cycle. Compared to diestrus, pregnancy increased TH levels in both superior cervical ganglia and adrenal gland. Pregnancy was also associated with decreased NET levels in the superior cervical ganglia, but increased levels in the adrenal gland. Relative to diestrus, the pattern of changes of TH and the NET in rats during proestrus was generally similar to changes observed during pregnancy. To assess whether gonadal hormones were involved, ovariectomized rats were also studied and changes in serum estrogen and progesterone were assayed in a subset of animals in all groups. Variations in TH and the NET among all groups did not correlate with changes in either estrogen or progesterone, suggesting that the steroids were not exclusively responsible. In conclusion, reproductive status alters the expression of TH and the NET in adrenal gland and superior cervical ganglia of female rats, which could significantly influence the function of the sympathetic nervous system. However, the mechanism for these changes does not depend solely on changes in estrogen or progesterone.
TL;DR: Increased dietary salt can influence the activity of the sympathetic nervous system by suppressing the levels of tyrosine hydroxylase and the norepinephrine transporter, which may occur in vivo only in severe pathophysiological states, but not during increases in dietary salt without the synergistic effect of other factors.
Abstract: The present study tested the hypothesis that, in normal male rats, chronic changes in salt intake alter the levels of tyrosine hydroxylase and the norepinephrine transporter in sympathetic ganglia. Increasing dietary salt (from 0.02% to 1%, 4% or 8% NaCl in rat chow) decreased (p<0.05) the mRNA levels of tyrosine hydroxylase and the norepinephrine transporter in the adrenal gland, superior cervical ganglia and celiac ganglia. In addition, tyrosine hydroxylase and norepinephrine transporter protein levels were decreased (p<0.05) in the adrenal gland. To test the hypothesis that NaCl acts directly on postganglionic neurons to suppress the expression of these proteins, it was determined if increases in NaCl concentrations, of a magnitude achieved during increases in dietary salt in vivo, suppress expression of tyrosine hydroxylase and the norepinephrine transporter in cultured sympathetic neurons in vitro. Increased dietary salt increased plasma NaCl concentrations each by up to 4-6 mEq l(-1) (p<0.05), with the greatest increases occurring at night when the rats consume most of their food. In addition, NaCl added to cultured neurons decreased tyrosine hydroxylase and norepinephrine transporter protein and mRNA levels, and norepinephrine uptake; however, the NaCl concentration increases required were 15-30 mEq l(-1). These data suggest that increased dietary salt can influence the activity of the sympathetic nervous system by suppressing the levels of tyrosine hydroxylase and the norepinephrine transporter. While increased NaCl levels can act directly on neurons to suppress these proteins, this action may occur in vivo only in severe pathophysiological states, but not during increases in dietary salt without the synergistic effect of other factors.
TL;DR: The results suggest that the integrity of the forebrain structure(s) are critical for compensatory and recompensatory responses to 'rapid' blood loss; and the midbrain structure is critical for the decompensatory response to progressive blood loss irrespective of rate.
Abstract: The haemodynamic response to a fixed volume haemorrhage passes through three distinct phases: a normotensive, compensatory phase; a hypotensive, decompensatory phase; and a post-haemorrhage, recompensatory phase. The role of the forebrain and midbrain in regulating the triphasic response to a ‘fast’ (1.5%/min) or ‘slow’ (0.75%/min) rate of blood withdrawal (30% haemorrhage) was evaluated by comparing, in unanaesthetised rats, the effects of pre-collicular (PCD) vs. pre-trigeminal decerebrations (PTD). It was found that pre-trigeminal decerebration attenuated the decompensatory (hypotensive) phase to either a fast or slow haemorrhage. In contrast, pre-collicular decerebration attenuated the compensatory and recompensatory phases of the response to a ‘fast’ (but not a slow) haemorrhage. These results suggest that the integrity of (i) forebrain structure(s) are critical for compensatory and recompensatory responses to ‘rapid’ blood loss; and (ii) midbrain structure(s) are critical for the decompensatory response to progressive blood loss irrespective of rate.