Showing papers in "Journal of The Autonomic Nervous System in 1998"
Journal Article•
TL;DR: The clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction, are described and criteria to define the relative importance of these features are set.
Abstract: We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.
1,339 citations
TL;DR: The results suggest that different intravenously administered anesthetics affect the peripheral sympathetic outflows in qualitatively and quantitatively different manners.
Abstract: The effects of pentobarbital sodium, chloralose, and urethane on sympathetic nerve activity and arterial baroreceptor reflex were examined using rats chronically instrumented for recordings of blood pressure (BP), electrocardiogram and renal sympathetic nerve activity (RSNA). Pentobarbital sodium (30 mg/kg, i.v.) produced a decrease in BP with a transient decrease in heart rate (HR) and no change in RSNA. Chloralose (50 mg/kg, i.v.) also caused a decrease in BP and no change in HR and RSNA until a later increase in HR and RSNA, while urethane (800 mg/kg, i.v.) increased BP, HR, and RSNA. Baroreceptor reflex function was assessed by constructing a logistic function curve compiled from data obtained by intravenous infusion in increasing doses of phenylephrine and sodium nitroprusside. Both pentobarbital sodium and chloralose administration decreased the gain of baroreceptor reflex control of both HR and RSNA. Urethane also decreased the gain of baroreceptor reflex control of HR but elicited no change in that of RSNA. These results suggest that different intravenously administered anesthetics affect the peripheral sympathetic outflows in qualitatively and quantitatively different manners.
180 citations
TL;DR: It is suggested that insulin-dependent diabetes mellitus is associated with time-dependent reductions in resting heart rate and autonomic nervous control of cardiac function.
Abstract: Diabetes-associated alterations in resting heart rate and blood pressure have been demonstrated in clinical studies and in animal models of insulin-dependent diabetes mellitus (IDDM) These alterations may result from changes in the heart, vasculature or autonomic nervous system control Using the streptozotocin- (STZ-) treated rat model of IDDM, the current study was designed to: (1) monitor changes in heart rate and blood pressure continually during a 10-week period in conscious unrestrained animals; and (2) determine if observed alterations in heart rate were mediated by changes in sympathetic and/or parasympathetic nervous control Biotelemetry techniques were used Heart rate and blood pressure were recorded 24 h a day at 10 min intervals before and after induction of diabetes Diabetes was induced by iv administration of 50 mg/kg STZ Resting autonomic nervous system tone was estimated by chronotropic responses to full-blocking doses of nadolol (5 mg/kg ip) and atropine (10 mg/kg ip) STZ-induced diabetes was associated with time-dependent reductions in heart rate and its circadian variation Diastolic blood pressure and mean arterial pressure did not differ significantly when compared between control and STZ-treated animals; however, pulse pressure was diminished in diabetic rats Chronotropic responses to both nadolol and atropine were blunted significantly in diabetic animals suggesting that resting levels of both vagal and sympathetic nervous tone to the heart were diminished Heart rate in the presence of both nadolol and atropine was also decreased in diabetic rats All effects observed following administration of STZ were reversed, at least in part, by insulin treatment These results suggest that IDDM is associated with time-dependent reductions in resting heart rate and autonomic nervous control of cardiac function
118 citations
TL;DR: Afferent nerve signals were recorded from a peripheral cut end of the small nerve bundle innervating the white adipose tissue of the epididymis in the anesthetized rat to suggest the existence of leptin sensors in WAT which send afferent signals from the WAT to the central nervous system and evoke a reflex activation of sympathetic outflow to the Wat which may accelerate lipolysis.
Abstract: Afferent nerve signals were recorded from a peripheral cut end of the small nerve bundle innervating the white adipose tissue (WAT) of the epididymis in the anesthetized rat. An injection of leptin (2 ng, 0.2 ml) into the white adipose tissue facilitated the afferent activity. The response was dose dependent and the least effective dose was 100 pg (0.1 ml). An injection of 2 ng (0.2 ml) leptin into the one side of the WAT resulted in a reflex activation of efferent activity of the sympathetic nerve innervating the WAT of the bilateral epididymis. The observations suggest the existence of leptin sensors in WAT which send afferent signals from the WAT to the central nervous system and evoke a reflex activation of sympathetic outflow to the WAT which may accelerate lipolysis. This WAT to WAT reflex can explain a part of the effect of leptin on metabolic function of the fatty tissue such as the reduction of body weight and increase in energy expenditure as a negative feed-back reflex response.
109 citations
TL;DR: Data suggest that although NOS is seen in several trigeminal ganglion cells and coexists with CGRP in a subpopulation of the sensory neurons, its role in trigeminally mediated vasodilatation was not significant.
Abstract: Nitric oxide (NO) is a novel neurotransmitter candidate to which a large number of physiological roles has been ascribed. In the present study, immunocytochemistry was used to demonstrate NO synthase (NOS) and to investigate possible co-localization with other neurotransmitters. In the trigeminal ganglion of the cat, a moderate number of NOS immunoreactive nerve cell bodies was seen, of which the major part also expressed calcitonin gene-related peptide (CGRP). The nerve cell bodies expressing NOS in the trigeminal ganglion were predominantly of small to medium size; while numerous cell bodies of varying size contained CGRP. With in situ hybridization using oligonucleotide probes, CGRP mRNA was demonstrated in almost all trigeminal neurons of the cat. Stimulation of the nasociliary nerve resulted in a frequency-dependent increase in ipsilateral local cortical blood flow by 30±6%. Administration of the NOS inhibitor N G -nitro- l -arginine-methylester ( l -NAME) did not significantly alter this response when applied intravenously or on the cortical surface. Local cortical administration of the CGRP blocker h-CGRP (8–37) did not alter the cerebral vasodilator response to hypercapnia or resting flow. However, the nasociliary nerve response was reduced by 50% after h-CGRP (8–37), with a general shift to the right of the frequency–response curve. These data suggest that although NOS is seen in several trigeminal ganglion cells and coexists with CGRP in a subpopulation of the sensory neurons, its role in trigeminally mediated vasodilatation was not significant.
104 citations
TL;DR: Different levels of lesion and the resulting interruption to sympathetic pathways in the spinal cord are decisive factors in the degree of impairment of sympathetic innervation in SCI persons.
Abstract: Spinal cord lesion leads to an interruption of pathways from brain to the peripheral sympathetic nervous system, which results in pathological changes in sympathetic innervation. Free epinephrine (E), norepinephrine (NE) and dopamine (DA) were measured in 30 tetraplegics (TETRA), 15 high-lesion paraplegics (T1 and T4, HPARA), 15 paraplegics with injuries between T5 and T10 (MPARA), 15 low-lesion paraplegics (below T10, LPARA) and 16 non-handicapped control persons (C) at rest, at 60 and 100% of maximal oxygen consumption during graded wheelchair ergometry (WCE). The TETRA showed significant lower E and NE levels at rest and only slight increases during physical exercise. The E and NE concentrations of the paraplegics with a lesion below T5 were significantly higher than those of the high-lesion paraplegics, as well as those of the control persons at every point in the study. All paraplegics and the control persons showed, at submaximal and maximal exercise, a significant increase in NE. Only a slight increase in E in HAPRA was shown. No differences were found at rest and during exercise in E and NE levels in the MPARA and LPARA. No significant differences were found in the dopamine concentration at rest or during exercise for any of the groups. In summary, different levels of lesion and the resulting interruption to sympathetic pathways in the spinal cord are decisive factors in the degree of impairment of sympathetic innervation in SCI persons. Tetraplegics show less preganglionic resting activity because of interruption of impulses from central centers and no considerable stimulation of the sympathetic nervous system during maximal exercise. Individuals with high paraplegia have a partial impairment of catecholamine release, especially of epinephrine, at rest and during exercise. Paraplegics with a lesion level below T5 showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity in comparison to control persons.
103 citations
TL;DR: Anterograde tracing with the carbocyanine tracer DiI and the aminostyrol derivative DiA was used to selectively label fibers from the nucleus ambiguus, dorsal motor nucleus and nodose ganglion, respectively, terminating in the rat esophagus, and to compare them with the innervation of the gastric fundus in the same animals as discussed by the authors.
Abstract: Anterograde tracing with the carbocyanine tracer DiI and the aminostyrol derivative DiA was used to selectively label fibers from the nucleus ambiguus, dorsal motor nucleus and nodose ganglion, respectively, terminating in the rat esophagus, and to compare them with the innervation of the gastric fundus in the same animals. Ambiguus neurons terminated on motor endplates distributed mainly to the ipsilateral half of the esophagus. There was no evidence of preganglionic innervation of myenteric ganglia from ambiguus neurons. Neurons of the dorsal motor nucleus supplied sparse fibers to only about 10% of enteric ganglia in the esophagus while they innervated up to 100% of myenteric ganglia in the stomach. Neurons of the nodose ganglion terminated profusely on more than 90% of myenteric ganglia of the esophagus and on about 50% of ganglia in the stomach. Afferent vagal fibers were also frequently found in smooth muscle layers starting at the esophago-gastric junction. In contrast, they were extremely rare in the striated muscle part of the esophagus. These morphological data suggest a minor influence of neurons of the dorsal motor nucleus and a prominent influence of vagal afferent terminals onto myenteric neurons in the rat esophagus.
97 citations
TL;DR: The findings indicate the clinical potential of drugs such as clonidine, moxonidine and rilmenidine for chronically lowering portal venous pressure in cirrhosis and elucidation of the abnormalities in central nervous control of sympathetic outflow in heart failure has become clinically relevant.
Abstract: Although the underlying mechanisms no doubt differ, activation of the sympathetic nervous system is an important pathophysiological feature in primary arterial hypertension, in portal hypertension accompanying hepatic cirrhosis, and in heart failure, and is a logical therapeutic target for centrally acting sympathetic nervous system suppressant drugs. Portal hypertension: The sympathetic outflows to skeletal muscle vasculature, the heart, the kidneys and to the hepatomesenteric circulation are stimulated in patients with alcoholic cirrhosis of the liver, perhaps as a reflex response to the vasodilatation and vascular shunting present. Acute dosing with clonidine produces dose dependent reduction in noradrenaline spillover from visceral organs and reduction in hepatic vein wedge pressure, with preservation of hepatic blood flow and negligible fall in arterial pressure. These findings indicate the clinical potential of drugs such as clonidine, moxonidine and rilmenidine for chronically lowering portal venous pressure in cirrhosis. Arterial hypertension: Activation of the sympathetic outflow to the heart, kidneys and skeletal muscle vasculature is commonly present in younger (< 45 years) patients with essential hypertension. The sympathetic stimulation appears to have adverse consequences in hypertensive patients beyond blood pressure elevation. Neural vasoconstriction in skeletal muscle has metabolic effects by impairing glucose delivery, which is a basis for insulin resistance and hyperinsulinemia. Within the heart a trophic effect of sympathetic activation on cardiac growth, contributing to the development of left ventricular hypertrophy, and an arrhythmogenic effect are also likely. Cardiac failure: The cardiac sympathetic nerves are preferentially stimulated in severe heart failure, with norepinephrine release from the failing heart at rest being increased as much as 50-fold, similar to the level seen in healthy people during near maximum exercise. This preferential activation of the cardiac sympathetic outflow contributes to arrhythmogenesis and possibly to progression of the heart failure, and has been directly linked to mortality; a high rate of spillover of noradrenaline from the heart is a strong, independent predictor of poor prognosis in severe cardiac failure. The mechanisms underlying sympathetic nervous stimulation are not entirely clear. Increased intracardiac diastolic pressure seems to be one peripheral signal, and increased forebrain norepinephrine turnover an important central mechanism. Following the demonstration of the beneficial effect of the beta-adrenergic blocker, carvedilol, and with second generation centrally acting sympathetic suppressants now under clinical investigation, elucidation of the abnormalities in central nervous control of sympathetic outflow in heart failure has become clinically relevant.
83 citations
TL;DR: Parasympathetic ganglia located in the CMV fat pad mediated a decrease in ventricular contractility during vagal stimulation, which had no effect on vagally-mediated slowing of sinus rate or AV conduction.
Abstract: We hypothesized that selective control of ventricular contractility might be mediated by postganglionic parasympathetic neurons in the cranial medial ventricular (CMV) ganglion plexus located in a fat pad at the base of the aorta. Sinus rate, atrioventricular (AV) conduction (ventricular rate during atrial pacing), and left ventricular contractile force (LV dP/dt during right ventricular pacing) were measured in eight chloralose-anesthetized dogs both before and during bilateral cervical vagus stimulation (20-30 V, 0.5 ms pulses, 15-20 Hz). Seven of these dogs were tested under beta-adrenergic blockade (propranolol, 0.8 mg kg(-1) i.v.). Control responses included sinus node bradycardia or arrest during spontaneous rhythm, high grade AV block or complete heart block, and a 30% decrease in contractility from 2118 +/- 186 to 1526 +/- 187 mm Hg s(-1) (P 0.05) decrease in contractility but still elicited the same degree of sinus bradycardia and AV block (N = 8, P < 0.05). Five dogs were re-tested 3 h after trimethaphan fat pad injection, at which time blockade of vagally-induced negative inotropy was partially reversed, as vagal stimulation decreased LV dP/dt by 19%. The same dose of trimethaphan given either locally into other fat pads (PVFP or IVC-ILA) or systemically (i.v.) had no effect on vagally-induced negative inotropy. Thus, parasympathetic ganglia located in the CMV fat pad mediated a decrease in ventricular contractility during vagal stimulation. Blockade of the CMV fat pad had no effect on vagally-mediated slowing of sinus rate or AV conduction.
80 citations
TL;DR: It was found that rhythms with the same basic frequencies may not only appear simultaneously, but also at various times in the different functional systems, including the cardiovascular system and peripheral functional systems.
Abstract: Several neurons from different regions of the brainstem of anesthetized dogs were simultaneously recorded, together with various parameters of the cardiovascular system, respiration, efferent sympathetic neural activities and cortical activity. Often rhythmic changes of activity in the range 0.05–0.5 Hz could be observed in the simultaneously recorded signals. The rhythms were analysed in time domain and by power spectra and their changes depicted over the time. The most striking rhythms between 0.05 Hz and 0.5 Hz are the respiratory rhythm and those rhythms that originate in reticular neurons of the common brainstem system as well as their respective harmonics, i.e. the ranges around the integer multiple frequencies of these basic rhythms. The observed oscillations can vanish and reappear at times. Frequencies of basic oscillations and harmonics and their amplitudes are subject to distinct slow modulations. These modulations can have irregular as well as regular courses. The different rhythms can appear separately or simultaneously in the single signals. The most important phenomenon to be observed is that the rhythms mutually influence their frequencies, which follows the rules of `relative coordination' as described by E. v. Holst. Such changes of rhythmic activities generally also concern the ranges of harmonics of the basic rhythms. Rhythmic influences on peripheral functional systems, e.g. the cardiovascular system, are most distinct at times when the different rhythms overlap in their frequency ranges. This holds not only for the ranges of basic frequencies, but also for the ranges of their harmonics. Further it was found that rhythms with the same basic frequencies may not only appear simultaneously, but also at various times in the different functional systems. The temporal course of changes of these rhythms, their interactions and their influence on the processing of cardiac rhythmic neuronal discharge patterns is demonstrated. The meaning of the mutually influencing rhythms for the functional organization of central nervous structures is discussed.
79 citations
TL;DR: The latter method showed similar diagnostic value concerning the CAN as the classical Ewing standard battery of cardiovascular function tests, although its application proved to be shorter, less stressful and more independent from patient cooperation.
Abstract: Our aim was to select those parameters of heart rate variability (HRV) within its short-term power spectral analysis (PSA), which have a capability similar to that of the standard Ewing battery of cardiovascular function tests in determining different degrees of cardiovascular autonomic neuropathy (CAN) in diabetes and to compare the usefulness of both methods for diagnostic purposes in the everyday routine. Commonly used standard battery of cardiovascular autonomic function tests evaluated as total Ewing score as well as short-term PSA of HRV were used in 119 diabetic patients (age: 52.7 +/- 9.8, diabetes duration: 22.2 +/- 12.7 years). From this cohort, patients were selected according to the total Ewing score by matching for age, gender, BMI and diabetes type for 3 groups, each of 17 patients, with no CAN (total Ewing score 0-0.5), with early involvement (score 1.0-2.5) and with definite or severe CAN (score 3.0-5.0). Short-term PSA of HRV performed in three positions (supine1-standing-supine2) included frequency-domain and time-domain parameters of HRV. Cumulative spectral power of total frequency band (0.06-0.50 Hz) and spectral power of low-frequency band (0.06-0.15 Hz) during both supine positions proved to be the most selective and discriminating among all patient groups in inter-group comparison and in analysis of discriminance. The correlation between the total Ewing score and the cumulative spectral power of total frequency band was r = -0.87 (P < 0.001). About 83.2% of cases classified by short-term PSA of HRV using the variables selected by analysis of discriminance was congruent with the classification by the total Ewing score alone. Time expenditure for the performance of each examination was 31 +/- 10 min for Ewing test battery vs. 14 +/- 2 min for short-term PSA of HRV (P < 0.001). In summary, the latter method showed similar diagnostic value concerning the CAN as the classical Ewing standard battery of cardiovascular function tests, although its application proved to be shorter, less stressful and more independent from patient cooperation. Cumulative spectral power of total frequency band (LFHF cumpower) can be used for overall description of the degree of cardiac denervation in diabetes while using short-term PSA of HRV.
TL;DR: It is suggested that MCs arise from presynaptic suppression of ongoing inhibitory neurotransmitter release, and the cyclical attenuation in the amplitude of the non-nitrergic IJP does not arise from cyclical postjunctional changes in membrane resistance or potential.
Abstract: Intracellular microelectrodes were used to record electrically evoked inhibitory junction potentials (IJPs) and electrotonic potentials during spontaneous cyclical depolarisations (myoelectric complexes, MCs) in the circular muscle layer of mouse colon in vitro. In the presence of nifedipine (1-2 microM) and atropine (1 microM), MCs were recorded every 264 +/- 18 s. Between MCs, single electrical stimuli (15 V, 0.6 ms, every 8 s) elicited IJPs whose amplitudes remained constant. In comparison, during the depolarising phase of MCs, the mean IJP amplitude was reduced by 61 +/- 7%, while during the late plateau and early repolarising phase of MCs, IJP amplitude was increased (up to 20%). NG-nitro-L-arginine (NOLA, 100 microM) abolished the repolarisation phase between MCs, so that the circular muscle remained depolarised and the amplitude of MCs was reduced by 73 +/- 6%. However, the amplitude of evoked IJPs was unaffected, as was the decrease in their amplitude during the depolarising phase of the residual MCs. In the presence of NOLA (100 microM), the further addition of apamin (250 nM) reduced the amplitude of evoked IJPs by approximately half. However, the amplitudes of NOLA- and apamin-resistant IJPs were also attenuated by 82 +/- 5% during the depolarising phase of residual MCs (amplitude: 1.9 +/- 1 mV). However, during this phase, the amplitude of an electrotonic potential (evoked by extracellular current application) was not attenuated. Addition of hexamethonium (500 microM), or tetrodotoxin (TTX) (1.6 microM) to solutions containing NOLA and apamin were without effect on membrane potential, but the residual MCs and the cyclical attenuation in IJP amplitude were abolished. During the intervals between MCs, membrane potential is maintained under tonic inhibition, via spontaneous release of inhibitory neurotransmitter(s), predominantly through nitrergic mechanisms. The cyclical attenuation in the amplitude of the non-nitrergic IJP does not arise from cyclical postjunctional changes in membrane resistance or potential. Moreover, the generation of the depolarising phase of MCs involves the simultaneous suppression of both nitrergic and non-nitrergic inhibitory neurotransmission. It is suggested that MCs arise from presynaptic suppression of ongoing inhibitory neurotransmitter release.
TL;DR: Clarification of its role in normal brain function, however, has not yet been fully established, in part because of the absence of agents that selectively affect its biosynthesis or degradation.
Abstract: Agmatine, which in other life forms serves as a metabolic intermediate for polyamine biosynthesis, appears to have properties in mammals consistent with its actions as a neurotransmitter/neuromodulator. Thus, agmatine is synthesized unequally in brain by arginine decarboxylase (ADC); is stored in neurons and axon terminals with a heterogeneous distribution; is released from synaptosomes by depolarization; is enzymatically converted by agmatinase to putrescine; interacts not only with alpha2-adrenergic and I-receptors in the CNS, but also may selectively block NMDA receptor channels; and, when administered centrally, has several potent biological actions. Clarification of its role in normal brain function, however, has not yet been fully established, in part because of the absence of agents that selectively affect its biosynthesis or degradation.
TL;DR: Initial bradycardia after DXM is mediated via the baroreflex, and HR reductions may result mainly from central sympathetic depression, which is likely to be attributable to its peripheral vascular effects including the stimulation of pre-synaptic alpha2-adrenoceptors, rather than to central sympathetic depressed effects.
Abstract: To clarify the role of the neural blood pressure control system in hemodynamic changes after dexmedetomidine (DXM) administration, we examined the effects of an intravenous injection of DXM (10 microg/kg) on heart rate (HR), mean blood pressure (MBP), central venous pressure (CVP) and renal sympathetic nerve activity (RNA) in urethane-anesthetized rabbits using direct recordings of RNA. The animals were divided into four groups: animals with an intact neuraxis (intact group; n = 12), cervical vagotomized animals (vagotomy group; n = 5), sino-aortic denervated animals (SAD group; n = 5), and animals with SAD plus vagotomy (SADV group; n = 5). An initial HR decrease, which occurred in the intact group, did not occur in the other three groups, suggesting the mediation of the baroreflex. A subsequent HR decrease occurred in the three groups other than the vagotomy group, in which RNA recovered earlier than in the other groups. RNA in the intact group, associated with transient hypertension, was suppressed shortly after the injection. Such an RNA drop was not eliminated even in the SADV group. Despite recovery of RNA, hypotension lasted until the end of experiment in the intact and vagotomy groups. However, sustained depression of RNA associated with lasting hypotension was found in the SAD and SADV groups. CVP in all groups did not change significantly after the injection. These results suggest the following: (1) Initial bradycardia after DXM is mediated via the baroreflex. Subsequently, HR reductions may result mainly from central sympathetic depression. (2) An initial reduction in RNA is not mediated via the baroreceptor reflex, unlike HR responses, but by central sympatho-inhibitory effects. (3) Long-lasting hypotension after DXM is likely to be attributable to its peripheral vascular effects including the stimulation of pre-synaptic alpha2-adrenoceptors, rather than to central sympathetic depression.
TL;DR: Small changes in RSNA, irrespective of the stimulus, modulate renal blood flow and the role of the renal nerves in these responses and in providing a tonic level of vasoconstriction within the kidney was demonstrated.
Abstract: Renal sympathetic nerve activity (RSNA) is postulated to influence renal function in selective ways with changes in renal hemodynamics only occurring during high stimulus intensities. The aim of this study was to determine the renal blood flow (RBF) response to a number of stimuli designed to increase RSNA by a modest amount and assess the possibility that different afferent stimuli produce differential levels of vasoconstriction by differentially altering the pattern of RSNA. Experiments were performed in eight conscious rabbits subjected to 20 min periods of three stimuli noise stress, air jet stress or hypoxia (10% O2). RSNA was significantly increased 12 +/- 4, 31 +/- 8 and 14 +/- 5% (means of 20 min periods +/- SEM) and these effects were mirrored in the significant changes in RBF over the period of each stimuli with mean reductions of 8 +/- 1, 10 +/- 3 and 8 +/- 4% during noise, air jet stress and hypoxia respectively. Changes in plasma renin activity did not occur without changes in RBF. With regard to the pattern of RSNA discharges, hypoxia selectively increased the amplitude (number of recruited nerves) while noise and air jet stress increased both the amplitude and frequency of discharges. The role of the renal nerves in these responses and in providing a tonic level of vasoconstriction within the kidney, was demonstrated in experiments on a group of eight renal denervated animals. The renal denervated rabbits had greater resting RBF than the intact rabbits (54 +/- 1 denervated vs. 38 +/- 1 ml min(-1) intact), and RBF was not altered by any of the afferent stimuli. We conclude that small changes in RSNA, irrespective of the stimulus, modulate renal blood flow.
TL;DR: It is suggested that vagal afferents have a protective role in TNBS-induced colitis in rats, unrelated to changes in colonic transit time.
Abstract: The aim of this study was to evaluate the regulatory role of vagal afferents in the development of colonic inflammation induced by trinitrobenzenesulfonic acid (TNBS) in rats. Groups of Wistar rats were treated with capsaicin or its vehicle applied perivagally (sham treatment). Colonic transit time was evaluated, and, two days later, one half of the animals received an intracolonic instillation of TNBS/ethanol (40 mg/kg), and the other received saline. Inflammation was evaluated functionally (gut permeability), biochemically (myeloperoxydase activity) and histologically. Vagal capsaicin deafferentation did not modify colonic transit time. In TNBS treated groups, inflammation was enhanced by capsaicin pretreatment, as determined by an increased gut permeability, MPO activity, and histological damage score. These results suggest that vagal afferents have a protective role in TNBS-induced colitis in rats, unrelated to changes in colonic transit time.
TL;DR: There was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone, and the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms.
Abstract: Pain sensitivity decreases with increasing resting blood pressure. This blood pressure-pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception. To test this hypothesis, we measured mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), muscle sympathetic nerve activity (MSNA), serum catecholamines, and individual pain rating scales during 2 min periods of noxious mechanostimulation (skin fold pinching) in nine young (26 +/- 2 year), male normotensive (NT) subjects and in 12 age and weight matched males with borderline hypertension (BHT). Measurements were performed before and after the i.v. administration of naloxone (0.15 mg/kg) and placebo in a randomized double-blind cross-over trial. In the pre-naloxone trials, pain led to similar changes in MAP, CVP, MSNA and plasma catecholamines in the two groups except for a higher increase in HR in the BHT group as compared to the NT group (3 +/- 1 vs. 1 +/- 1 bpm; P < 0.005). Opioid blockade with naloxone increased MSNA responses to pain in the NT group (from 5 +/- 1 to 9 +/- 1 bursts/min, and, from 100 +/- 23 to 204 +/- 36 units/min, respectively; P < 0.05) but did not significantly affect the MSNA response to pain in the BHT group. Pain induced responses of MAP, CVP, and catecholamines were not altered by naloxone in either group. Overall, there was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone. The BHT subjects exhibited a lower pain perception compared to the NT subjects (P < 0.005). Naloxone increased pain rating in the NT group (from 194 +/- 9 to 218 +/- 13; P < 0.005) but not in the borderline hypertensive group (160 +/- 8 vs. 168 +/- 10; P = 0.36). Except for a decreased HR response in the BHT group, placebo had no effect on the responses to pain. Our data do not indicate a major role of the endogenous opioid system for the blood pressure-pain interaction in man. Endogenous opioids affect pain perception and sympathetic nerve activity responses to pain in normotensive men but their activity seems to be attenuated in borderline hypertensive subjects. Therefore, the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms.
TL;DR: Impaired baroreflex function for both heart rate and sympathetic nerve activity in the elderly is suggested.
Abstract: To determine whether the baroreflex control of sympathetic nerve activity is attenuated in the elderly, muscle sympathetic nerve activity (MSNA) from the tibial nerve was monitored using microneurography, and heart rate and blood pressure were recorded during the depressor (phase II) or pressor (phase IV) period to Valsalva's maneuver in 10 younger subjects and 7 aged subjects. The baroreflex slope for heart rate showed attenuation in the aged subjects during the pressor phase but not during the depressor phase, the baroreflex slope for MSNA was also attenuated in the aged subjects during the pressor and tended to be attenuated during the depressor phases. These data suggest impaired baroreflex function for both heart rate and sympathetic nerve activity in the elderly.
TL;DR: Not only is there considerable structural damage, chronic inflammation and mast cell infiltration to the lacrimal gland with ageing, but also possible redifferentiation of acini from serous to seromucous and then to mucous acini, suggest a reduction or an inability of the acini to synthesise and to secrete protein.
Abstract: This study investigates the differences in the outward appearance and morphology of lacrimal glands, the morphology within the lacrimal acinar cells and the secretion of protein from acinar cells of young (3–5 months) and aged (20 and 24 months) male rats. The appearance of the glands, as seen by the naked eye, differed between the three age-groups. The lacrimal gland of young animals was a smooth pink tissue, while the tissue from aged animals appeared lobular and white in colour, thought to result from infiltration of fatty/connective tissue. Glands from 24 month old animals had a more pronounced lobular appearance than the glands from 20 month old animals. Light microscopy studies revealed that as the animals aged there was evidence of progressive morphological changes. These changes included thickening of the connective tissue sheath, chronic inflammation with increased infiltration by mast cells, patchy destruction of ductal and vascular tissues, enlargement of lacrimal ducts, luminal swelling of the acini, and changes in acinar type. Electron microscopy (EM) studies revealed the presence of 3 types of acini in the rat lacrimal gland: acini which contained only protein secretory granules (serous acini), acini which contained protein and mucous secretory granules (seromucous acini), and acini which contained only mucous secretory granules (mucous acini). In young glands the majority of acini were serous with a few seromucous acini and even fewer mucous acini. In aged glands there were significant reductions in serous acini (ANOVA; P<0.01) when compared to the young glands. In 20-month-old glands, there were marked increases in the percentage occurrence of seromucous acini, while in 24 month old glands, there were large increases in the relative number of mucous acini. Qualitative EM studies demonstrated that the typical acini from young glands contained numerous protein secretory granules. Ageing was associated with a progressive loss of protein (serous) secretory granules. Furthermore, marked changes and patchy destruction of the endoplasmic reticulum and Golgi apparatus were observed in acini of glands from aged rats when compared to acini of glands from young rats. Measurement of total protein output from acini revealed a significant (Student's t-test, P<0.05) decrease in protein secretion from aged glands compared to glands from young animals. These results suggest that not only is there considerable structural damage, chronic inflammation and mast cell infiltration to the lacrimal gland with ageing, but also possible redifferentiation of acini from serous to seromucous and then to mucous acini. Furthermore, the results also suggest a reduction or an inability of the acini to synthesise and to secrete protein from glands of aged animals compared to glands of young rats. All of these changes appear to occur more rapidly as the rats mature between 20 and 24 months. These findings provide a morphological basis to explain the phenomenon of reduced tear/protein secretion with ageing.
TL;DR: The data suggest that endogenous NO plays an inhibitory role in cardiac sympathetic neurotransmission, but there was no convincing evidence from the results for a major role for endogenous NO in vagal control of heart rate, with or without prior adrenergic stimulation.
Abstract: The role of nitric oxide (NO) in the sympatho-vagal control of heart rate was investigated in the cardiac sympathectomized and vagotomized anaesthetised rabbit and in the isolated guinea-pig atria with intact vagus nerve. Specific inhibition of neuronal nitric oxide synthase (nNOS) with 1-(2-trimethylphenyl) imidazole (TRIM, 50 mg kg−1 i.v. in vivo) significantly enhanced the magnitude of the change in heart rate (HR) with sympathetic nerve stimulation (SNS, 31.6±4.5 bpm control vs. 49.7±6.0 bpm in TRIM, P<0.05, 10 Hz). This effect was reversed by l-arginine (ΔHR 37.2±4.1 bpm, 50 mg kg−1 i.v.). An enhanced HR response to SNS was also seen with the non-isoform specific inhibitor, N-ω-nitro-l-arginine (l-NA, 50 mg kg−1 i.v.). Infusing isoprenaline (0.2 μg kg−1 min−1) did not mimic the change in HR response to SNS with TRIM. There was, however, no significant effect of inhibition of NOS with TRIM l-NA or NG-monomethyl-l-arginine (l-NMMA, 20 mg kg−1 i.v.) on the magnitude of the change in HR with vagal nerve stimulation (5 Hz) in vivo. There was also no significant effect of NOS inhibition on the change in HR with vagal nerve stimulation in vivo in the presence of pre-adrenergic stimulation or in the presence of propranolol (0.5 mg kg−1 i.v., 2, 5 and 10 Hz stimulation). This result was confirmed in the isolated guinea-pig atria with the specific nNOS inhibitor, 7-nitroindazole (7-NiNa, 100 μM) at 1, 2, 3 or 5 Hz stimulation frequency. Our data suggest that endogenous NO plays an inhibitory role in cardiac sympathetic neurotransmission, but there was no convincing evidence from our results for a major role for endogenous NO in vagal control of heart rate, with or without prior adrenergic stimulation.
TL;DR: There is indeed a close nexus between 'presynaptic' imidazoline receptors on noradrenergic terminals and 'downstream' alpha2-adrenoceptors within the rostral ventrolateral medulla (RVLM), and this hypothesis brings together opposing points of view that the mechanism for hypotension must involve either the imidrazoline receptor or thealpha2- adrenoceptor.
Abstract: Since the first suggestion of the existence of imidazoline receptors, there has been a continuing and yet unresolved debate as to their contribution to the antihypertensive actions of clonidine-like agents. In this review we bring together a number of studies from our laboratory which have examined the importance and interdependence of imidazoline receptors and alpha2-adrenoceptors in the mechanism of action of centrally acting antihypertensive drugs. Using conscious rabbits and a range of imidazoline and specific alpha2-adrenoceptor antagonists we have consistently found that second generation agents rilmenidine and moxonidine preferentially act via imidazoline receptors but that alpha2-adrenoceptors are important for the hypotension produced by clonidine and alpha-methyldopa. Despite this difference in receptor mechanism, the hypotension produced by all these drugs is dependent on central noradrenergic pathways. In other studies using anaesthetised rabbits and direct measures of sympathetic nerve activity we confirmed the generally held view that the major site of sympatho-inhibitory actions and sympathetic baroreflex effects of centrally acting antihypertensive agents is the rostral ventrolateral medulla (RVLM). We also found, using microinjection of specific antagonists, that alpha2-adrenoceptors in this nucleus appear to be activated as a consequence of imidazoline receptor activation. Thus, there appears to be a close relationship between imidazoline receptors and alpha2-adrenoceptors located in the RVLM in mediating the hypotension and inhibition of renal sympathetic nerve activity. Furthermore in recent studies using a noradrenergic neurotoxin microinjected into the RVLM we found that this treatment selectively blocked the actions of moxonidine but not clonidine, suggesting that I1-imidazoline receptors may be located on adrenergic terminals in situ. By contrast, clonidine acts predominantly via alpha2-adrenoceptors, perhaps located on cell bodies in the nucleus. We conclude that there is indeed a close nexus between 'presynaptic' imidazoline receptors on noradrenergic terminals and 'downstream' alpha2-adrenoceptors within the RVLM. Our hypothesis brings together opposing points of view that the mechanism for hypotension must involve either the imidazoline receptor or the alpha2-adrenoceptor. Clearly both are important.
TL;DR: The results suggest that although phasic inputs from pulmonary and thoracic stretch receptors make a statistically significant contribution to respiratory sinus arrhythmia, that contribution is small.
Abstract: We studied the effects of mechanical lung inflation on respiratory frequency R-R interval and arterial pressure fluctuations in nine healthy young adults undergoing elective orthopedic surgery. We conducted this research to define the contribution of pulmonary and thoracic stretch receptor input to respiratory sinus arrhythmia. We compared fast Fourier transform spectral power during three modes of ventilation: (1) spontaneous, frequency-controlled (0.25 Hz) breathing, (2) intermittent positive pressure ventilation (0.25 Hz, with a tidal volume of 8 ml/kg) and (3) high frequency jet ventilation (5.0 Hz, 2.5 kg/cm2), after sedation and vecuronium paralysis. Mean R-R intervals, arterial pressures and arterial blood gas levels were comparable during all three breathing conditions. Respiratory frequency systolic pressure spectral power was comparable during spontaneous breathing and conventional mechanical ventilation, but was significantly reduced during high frequency jet ventilation (P < 0.05). Respiratory frequency R-R interval spectral power (used as an index of respiratory sinus arrhythmia) declined dramatically with sedation and muscle paralysis (P < 0.05), but was greater during conventional mechanical, than high frequency jet ventilation (P < 0.05). These results suggest that although phasic inputs from pulmonary and thoracic stretch receptors make a statistically significant contribution to respiratory sinus arrhythmia, that contribution is small.
TL;DR: The results suggest that generalised increases in the sympathetic discharge, causing increases in ABP, can prevent concomitant increases in CBF by acting on both small resistance and large compliant vessels.
Abstract: There is no general agreement regarding several aspects of the role of the sympathetic system on cerebral haemodynamics such as extent of effectiveness, operational range and site of action. This study was planned to identify the effect of a generalised sympathetic activation on the cerebral haemodynamics in healthy humans before it is masked by secondary corrections, metabolic or myogenic in nature. A total of 35 healthy volunteers aged 20–35 underwent a 5 min lasting cold pressor test (CPT) performed on their left hand. The cerebral blood flow (CBF) velocity in the middle cerebral arteries and arterial blood pressure were recorded with transcranial Doppler sonography and with a non-invasive finger-cuff method, respectively. The ratio of arterial blood pressure to mean blood velocity (ABP/ V m ) and Pulsatility Index (PI) were calculated throughout each trial. CPT induced an increase in mean ABP (range 2–54 mmHg depending on the subject) and only a slight, though significant, increase in blood velocity in the middle cerebral artery (+2.4 and +4.4% on ipsi- and contralateral side, respectively). During CPT, the ratio ABP/ V m increased and PI decreased in all subjects on both sides. These changes began simultaneously with the increase in blood pressure. The increase in ABP/ V m ratio is attributed to an increase in the cerebrovascular resistance, while the concomitant reduction in PI is interpreted as due to the reduction in the compliance of the middle cerebral artery. The results suggest that generalised increases in the sympathetic discharge, causing increases in ABP, can prevent concomitant increases in CBF by acting on both small resistance and large compliant vessels. This effect is also present when a slight increase in blood pressure occurs, which suggests a moderate increase in the sympathetic discharge, i.e. when ABP remains far below the upper limit of CBF autoregulation.
TL;DR: In conclusion, interstitial cells of Cajal are evenly distributed in the layers of the muscularis propria of the rectum, but have a lower density in the internal anal sphincter.
Abstract: The interstitial cells of Cajal are proposed to have a role in the control of gut motility. The aim of this study was to establish the distribution of interstitial cells of Cajal in the wall of the normal human anorectum. Interstitial cells of Cajal express the proto-oncogene c- kit . Interstitial cells of Cajal were identified in the colon by immunohistochemical staining, using a rabbit polyclonal anti-c- kit antibody. Anorectal tissue was obtained at surgical resection for carcinoma of the colorectum. Density of interstitial cells of Cajal was graded. Statistical analysis was performed using χ 2 tests. In the longitudinal and circular muscle layers of the rectum interstitial cells of Cajal were seen in the bulk of the muscle layer. In the intermuscular plane interstitial cells of Cajal encased the myenteric plexus. Interstitial cells of Cajal were found at the inner margin of the circular muscle and in association with neural elements of the submuscular plexus. Within the internal anal sphincter interstitial cells of Cajal were infrequently scattered among the muscle fibres. The density of interstitial cells of Cajal in the internal anal sphincter was significantly lower than that observed in the circular muscle layer of the rectum ( P =0.014). In conclusion, interstitial cells of Cajal areevenly distributed in the layers of the muscularis propria of the rectum, but have a lower density in the internal anal sphincter.
TL;DR: Sympathetic BRS was significantly lower during sleep than while subjects were awake in the evening, and it remained low after the subjects woke up in the morning, and this sympathetic BRS pattern may contribute to diurnal haemodynamic variables and may account, at least in part, for the connection between circadian rhythm and cardiovascular disease.
Abstract: To determine whether or not there are nocturnal variations in sympathetic baroreflex sensitivity (BRS), we measured spontaneous sympathetic BRSs in eight normal subjects (average 24.5 years old) between 2300 and 0700 h. Electrocardiogram, blood pressure, polysomnography, and muscle sympathetic nerve activity (MSA) using microneurography were recorded. We defined cardiac 'baroreflex sequences' as those that contain three or more adjacent pulses, with the systolic blood pressure and the subsequent pulse interval either continuously increased or decreased. A similar analysis was applied to sympathetic BRSs. We selected three or more adjacent pulses during which diastolic blood pressures continuously increased or decreased. Total activity in MSA was defined as burst per minute x burst amplitude and we calculated the regression coefficients between the diastolic blood pressure and the subsequent total activities in MSA. The regression coefficients were classified as either negative or positive ones. When they were less than zero, we termed them 'baroreflex sequences'. Cardiac and sympathetic BRSs were estimated from the average slope of the baroreflex sequences. Sympathetic BRS was significantly lower during sleep than while subjects were awake in the evening (P < 0.05), and it remained low after the subjects woke up in the morning (P < 0.05). Conversely, cardiac BRS had a tendency to increase during sleep in the night, but not statistically significant. This sympathetic BRS pattern may contribute to diurnal haemodynamic variables and may account, at least in part, for the connection between circadian rhythm and cardiovascular disease.
TL;DR: It is suggested that in preparations that exhibit MC cycling, membrane potential between MCs is maintained in a state of tonic inhibition, predominantly mediated by nitrergic mechanisms generated via spontaneously active inhibitory neurons.
Abstract: Intracellular electrophysiological techniques were used to record the spontaneous myoelectric activity in the circular muscle layer of an in vitro preparation of whole mouse colon. In 34 out of 58 preparations, spontaneous depolarisations (myoelectric complexes, MCs) were recorded cyclically, about every 4 min. In these preparations, apamin (250 nM) and NG-nitro-L-arginine (NOLA, 100 microM) depolarised the membrane potential between MCs by 8 mV or 13 mV, respectively. Tetrodotoxin (1.6 microM) abolished MCs and also induced depolarisation (17 mV). In the remaining 24 preparations, MCs were not recorded and the membrane potential was significantly depolarised compared to the membrane potential between MCs. NOLA (100 microM), apamin (250 nM) and tetrodotoxin (1.6 microM) were without significant effect on membrane potential. It is suggested that in preparations that exhibit MC cycling, membrane potential between MCs is maintained in a state of tonic inhibition, predominantly mediated by nitrergic mechanisms generated via spontaneously active inhibitory neurons. Apamin-sensitive channels may also be involved in the inhibition.
TL;DR: GABA can influence baroreceptor afferent integration through both pre- Synaptic and post-synaptic mechanisms, with MSNs being generally less sensitive than PSNs, and the effects of GABA(B) agonists are variable depending upon the level of afferent Integration.
Abstract: The inhibitory amino acid gamma amino butyrate (GABA) has been shown to profoundly alter the integration of arterial baroreceptor inputs within the nucleus of the solitary tract (NTS). However, the relative roles of the major GABA receptor subtypes, the GABA(A) and the GABA(B) receptors, in the modulation of monosynaptic compared to polysynaptic afferent transmission within the NTS remain uncharacterized. In anesthetized rats, three types of NTS neuron were identified by their responses to aortic depressor nerve (ADN) stimulation; monosynaptic neurons (MSNs), polysynaptic neurons (PSNs) and ADN non-evoked neurons (NENs). Selective GABA(A) and GABA(B) agonists were applied to these neurons using iontophoretic techniques. The endogenous ligand GABA (2 mM), the selective GABA(A) agonist muscimol (0.04 and 0.02 mM) and the GABA(B) agonist baclofen (10 mM) all inhibited the spontaneous discharge of MSNs, PSNs and NENs (P < 0.01 for each group). In addition, GABA, muscimol and baclofen also inhibited ADN evoked discharge in both MSNs and PSNs (P < 0.05 for each group). Both GABA and baclofen significantly inhibited ADN evoked discharge in PSNs to a greater extent than in MSNs (P < 0.05 for each comparison). Muscimol at both doses, however, similarly inhibited ADN evoked discharge in both MSNs and PSNs. Examination of action potential amplitude and co-iontophoretic application of glutamate and GABA agonists suggested that GABA and muscimol induced inhibition were likely to be post-synaptic in origin, while baclofen produced both pre-synaptic and post-synaptic inhibition, depending upon the cell. In conclusion, GABA can influence baroreceptor afferent integration through both pre-synaptic and post-synaptic mechanisms. Furthermore, the effects of GABA(B) agonists are variable depending upon the level of afferent integration, with MSNs being generally less sensitive than PSNs.
TL;DR: The results suggest that the c-kit receptor expressing cells or interstitial cells of Cajal (ICC) in the myenteric region of the three organs, and in the SMP of the colon, are poorly coupled with the bulk of circular muscle tissue by gap junctions, while ICC in the DMP and inThe circular muscle layer of the stomach couple well with the surrounding muscle tissue.
Abstract: The distribution of the c-kit receptor expressing cells and gap junction protein, connexin (Cx) 43 in the guinea-pig stomach (antrum), small intestine (jejunum) and colon (ascending) was studied by immunohistochemistry. The anti-c-kit protein immunopositive cells were regularly observed in the myenteric region throughout all three organs. The immunopositive cells were also sparsely distributed in the circular muscle layer of both the stomach and the colon, but not in the small intestine. They were densely located in the regions of the deep muscular plexus (DMP) of the small intestine and submuscular plexus (SMP) of the colon. In contrast, strong immunoreactivity to anti-Cx 43 antibody was observed in almost the entire thickness of the circular muscle layer of the stomach and the small intestine, but not in the colon. Dense immunoreaction deposits were observed in the region of the DMP and SMP. However, only very weak immunoreactivity to anti-Cx 43 antibody was detected in the myenteric region of all three organs. These results suggest that the c-kit receptor expressing cells or interstitial cells of Cajal (ICC) in the myenteric region of the three organs, and in the SMP of the colon, are poorly coupled with the bulk of circular muscle tissue by gap junctions, while ICC in the DMP and in the circular muscle layer of the stomach couple well with the surrounding muscle tissue.
TL;DR: It is suggested, that in the circular muscle layer of mouse colon, NO does not mediate the fast hyperpolarisations associated with spontaneous or evoked IJPs.
Abstract: Intracellular microelectrodes were used to record spontaneous and evoked inhibitory junction potentials (IJPs) from the circular muscle layer of an in vitro preparation of whole mouse colon. Membrane potential recordings were made from cells of the mid to distal region of colon at 36±1°C in a modified Krebs' solution that contained atropine (1 μ M) and nifedipine (1–2 μ M). Spontaneously occurring hyperpolarisations of irregular amplitude and frequency (range: up to 20 mV and 2 Hz) were recorded that were resistant to N G -nitro- l -arginine (NOLA, 100 μ M), but were abolished by tetrodotoxin (TTX, 1.6 μ M) or apamin (250 nM). These were considered to be spontaneous IJPs as a consequence of activity in inhibitory motor neurons. Single electrical stimuli (0.6 ms, 15 V), elicited a fast IJP, whose time course could be superimposed on spontaneous IJPs of similar amplitude. The amplitude of evoked IJPs was not depressed by NOLA (100 μ M). However, in NOLA (100 μ M), further addition of apamin (250 nM) significantly depressed the amplitudes of the evoked IJPs by 44%. NOLA- and apamin-resistant evoked IJPs were abolished by TTX (1.6 μ M). It is suggested, that in the circular muscle layer of mouse colon, NO does not mediate the fast hyperpolarisations associated with spontaneous or evoked IJPs. Apamin abolished spontaneous IJPs, but electrical stimuli evoked an IJP with apamin-sensitive and resistant components both of which were non-nitrergic in origin.
TL;DR: The observations that GDNF concentrations are high in the adult intestine suggest that this growth factor may be important for the maintenance of the adult ENS.
Abstract: Glial derived neurotrophic factor (GDNF) is essential for the development of the enteric nervous system (ENS). Although previous work has measured GDNF mRNA levels, little is known about the concentration of GDNF protein produced in developing or adult tissues. The aim of this study was to quantitate the concentration of GDNF protein in various tissues of the developing and adult rat and in adult human gut. A two site antibody immunoassay was used to quantitate GDNF using recombinant rat GDNF as a standard. In the adult rat gastrointestinal tract the intestine contained the highest concentration of GDNF while the stomach and esophagus have the lowest concentrations. The isolated muscular wall of the intestine has approximately four times the GDNF concentration of the intact intestine. Other tissues with smooth muscle such as the aorta and urinary bladder contain moderate GDNF concentrations. In contrast, GDNF is barely detectable in the adult kidney and liver. High concentrations of GDNF were also detected in human colon and jejunum. As development proceeds in the rat, there is a tendency for the concentration of GDNF to increase in the intestine but decrease in other tissues. Treatment of the jejunum with the cationic surfactant benzyldimethyltetradecylammonium chloride (BAC) results in an increase in the number of smooth muscle cells, a decrease in myenteric neurons, and an increase in the concentration of GDNF in homogenates of intestine. The observations that GDNF concentrations are high in the adult intestine suggest that this growth factor may be important for the maintenance of the adult ENS.