Showing papers in "American Journal of Physiology-regulatory Integrative and Comparative Physiology in 1987"
TL;DR: The effects of NPY on food intake were attenuated by peripherally administered bombesin and centrally administered corticotropin-releasing factor and calcitonin, and cholecystokinin failed to inhibit NPY-induced feeding, and NPY did not alter circulating glucose levels.
Abstract: Neuropeptide Y (NPY) is a potent stimulator of food and water intake in rats. NPY still increases food intake even after a 2-h delay in access to food after central injection. When two injections of NPY are given 2 h apart, the second injection produced a substantial increase in food intake. This suggests that tolerance to the NPY effect does not develop after a single injection of NPY. NPY increases moving and exploration in the absence of food when rats are in their home environment but not when tested in a novel environment. Following administration of NPY, rats preferred a high-carbohydrate diet over a high-fat or high-protein diet. Microinjections of NPY showed that active sites included the anterior ventromedial nucleus, paraventricular nucleus of the hypothalamus, and the posterior lateral hypothalamus. NPY was neither additive nor synergistic when coadministered with norepinephrine. Whereas norepinephrine-induced feeding was inhibited by adrenalectomy and vagotomy, these maneuvers had no effect on NPY-induced food intake. This provides further evidence that NPY does not exert its effects on food intake through an alpha-adrenergic mechanism. The effects of NPY on food intake were attenuated by peripherally administered bombesin and centrally administered corticotropin-releasing factor and calcitonin. Cholecystokinin failed to inhibit NPY-induced feeding. NPY did not alter circulating glucose levels. These studies provide further insights into the role of NPY as a stimulator of ingestive behaviors.
305Â citations
TL;DR: TNF, in addition to IL 1 and IFN, is an endogenous somnogen, and the fact that TNF and IL 1 as well as other immunoactive substances, e.g.,IFN, muramyl peptides, and endotoxin, enhance SWS suggests that SWS is linked to the immune response.
Abstract: The cytokines interleukin 1 (IL 1) and interferon (IFN) are immune response modifiers that are also pyrogenic and somnogenic. Tumor necrosis factor (TNF) (cachectin) is another pyrogenic monocyte product whose production can be elicited by somnogenic agents such as endotoxin. Human recombinant TNF (rTNF), therefore, was assayed for somnogenic activity. Intravenous (iv) or intracerebroventricular (ICV) injections of rTNF enhanced slow-wave sleep (SWS) and electroencephalographic slow-wave (0.5-4.0 Hz) activity. Recombinant TNF also suppressed rapid-eye-movement sleep (REM) and induced biphasic fevers whether given by intravenous or ICV injection. Responses to rTNF were compared with those elicited by human recombinant beta-IL 1 (rIL 1). Sleep responses elicited by rIL 1 were similar to those previously reported for native IL 1 and to those elicited by rTNF. However, unlike rTNF, rIL 1 induced monophasic fevers. Animal behavior and brain temperature changes that occur during the transition from one arousal state to another remained undisturbed after either rTNF or rIL 1 treatment. The fact that TNF and IL 1 as well as other immunoactive substances, e.g., IFN, muramyl peptides, and endotoxin, enhance SWS suggests that SWS is linked to the immune response. We conclude that TNF, in addition to IL 1 and IFN, is an endogenous somnogen.
270Â citations
TL;DR: The temporal isolation data account quantitatively for the timing of the afternoon siesta and suggest that malfunctions of the phasing of the circadian pacemaker may underlie the insomnia associated with sleep-scheduling disorders.
Abstract: The human circadian pacemaker modulates our desire and ability to fall asleep at different times of day. To study this circadian component of sleep tendency, we have analyzed the sleep-wake patterns recorded from 15 free-running subjects in whom the sleep-wake cycle spontaneously desynchronized from the circadian rhythm of body temperature. The analysis indicates that the distribution of sleep onsets during free run is bimodal, with one peak at the temperature trough and, contrary to previous reports, a second peak 9-10 h later. Furthermore, there are two consistent zones in the circadian temperature cycle during which normal subjects rarely fall asleep. We hypothesize that this bimodal rhythm of sleep tendency, revealed under free-running conditions, maintains the same fixed phase relation to the circadian temperature cycle during 24-h entrainment. This would imply that normally entrained individuals should experience a peak of sleep tendency in the midafternoon and a zone of minimal sleep tendency approximately 1-3 h before habitual bedtime. Our temporal isolation data thereby account quantitatively for the timing of the afternoon siesta and suggest that malfunctions of the phasing of the circadian pacemaker may underlie the insomnia associated with sleep-scheduling disorders.
236Â citations
TL;DR: All organ masses scale allometrically; larger lizards have relatively smaller livers, but larger hearts and thigh muscles, and individual variation in endurance correlates with individual differences in heart LDH and thigh CS and PK activities.
Abstract: Amphibolurus nuchalis were collected in central Australia during mid- (January) and late summer (March). Endurance time at 1 km/h on a motorized treadmill is greater in larger lizards, scaling as M...
207Â citations
TL;DR: Observations that the effects of CCK-8 on OXY release were attenuated by gastric vagotomy clearly demonstrate the existence of a sensitive neural link between the stomach and the neurohypophysis in the rat.
Abstract: Systemic administration of cholecystokinin octapeptide (CCK-8) prompts an abrupt increase in circulating levels of oxytocin (OXY) but not vasopressin (VP) in rats. The present study determined whether CCK-8 selectively stimulated OXY-secreting neurons in the hypothalamic supraoptic nucleus of pentobarbital-anesthetized male rats. Antidromically identified neurosecretory neurons were categorized into putative OXY- and VP-secreting cells on the basis of their firing patterns and response to peripheral baroreceptor activation. Of 36 OXY-secreting cells studied, 30 demonstrated a 50-200% increase in firing frequency within 2 min of administering CCK-8 by intravenous or intraperitoneal injection, whereas none of the eight VP-secreting neurons studied was activated. In related experiments, 4-10 ml of air were used to inflate an intragastric balloon in rats; 20 of 22 OXY-secreting neurons displayed an abrupt and readily reversible increase in firing frequency, whereas only 2 of 17 VP-secreting cells were activated. Gastric distension similarly elevated plasma OXY levels in unanesthetized rats with indwelling gastric cannulas. Together with previous findings that the effects of CCK-8 on OXY release were attenuated by gastric vagotomy, these observations clearly demonstrate the existence of a sensitive neural link between the stomach and the neurohypophysis in the rat.
190Â citations
TL;DR: Although osmotic and hemodynamic stimuli to vasopressin release do not act independently of each other, the precise subtle interactions between them and other nonosmotic stimuli remain to be clarified.
Abstract: The functional characteristics of osmoregulated vasopressin secretion can be defined in terms of an osmotic threshold for its release and a sensitivity of the osmoreceptor and vasopressin-secreting unit. Osmotically stimulated thirst has features similar to osmoregulated vasopressin. There are wide individual variations in the functional characteristics of both thirst and vasopressin release in healthy humans, probably genetic in origin. The influence of aging appears to enhance the sensitivity of vasopressin secretion but blunt thirst appreciation. Yet in many physiological situations changes in osmoregulated vasopressin release and thirst occur in parallel. The fall in plasma osmolality associated with human pregnancy is accounted for entirely by a lowering of the osmotic thresholds for thirst and vasopressin release. Similar but less marked alterations accompany the ovulatory luteal phase of the menstrual cycle. A major nonosmotic stimulus to vasopressin secretion is hypotension and/or hypovolemia, mediated by high- (carotid sinus) and low- (left atrial) pressure receptors. Circulating catecholamines influence the release of vasopressin by alpha- and beta-adrenergic pathways. Drinking by hypertonic humans provides immediate reduction in thirst and vasopressin secretion probably mediated by pathways from the oropharynx. The modest but variable rise in plasma vasopressin in response to hypoglycemia appears to be due to cellular neuroglycopenia and is independent of parasympathetic pathways. Although osmotic and hemodynamic stimuli to vasopressin release do not act independently of each other, the precise subtle interactions between them and other nonosmotic stimuli remain to be clarified.
166Â citations
TL;DR: The results indicate that the CVM contains an obligatory synapse in the central aortic baroreflex pathway; neural transmission of aortIC baroreceptor information in the C VM is mediated by activation of NMDA receptors; and the neurotransmitter released at CVM synapses may be an excitatory amino acid.
Abstract: The purpose of this study was to identify central nervous system pathways and synaptic receptors that participate in baroreflex control of arterial pressure. Microinjections of excitatory amino acids into the caudal ventrolateral medulla (CVM) of anesthetized rats evoked depressor responses analogous to baroreceptor reflexes. Functional inactivation of CVM neurons produced by microinjection of the gamma-aminobutyric acid receptor agonist muscimol completely abolished baroreflex-mediated decreases in arterial pressure elicited by electrical stimulation of the aortic nerve and markedly reduced depressor responses produced by the excitatory amino acid L-glutamate. In contrast, selective blockade of N-methyl-D-aspartic acid (NMDA) receptors in the CVM abolished synaptically mediated depressor responses evoked by aortic nerve stimulation but not those elicited by L-glutamate, kainic acid, or quisqualic acid injected at the same site. These results indicate that the CVM contains an obligatory synapse in the central aortic baroreflex pathway; neural transmission of aortic baroreceptor information in the CVM is mediated by activation of NMDA receptors; and the neurotransmitter released at CVM synapses may be an excitatory amino acid.
165Â citations
TL;DR: In the studies reported here, intracerebroventricular administration of porcine NPY increased eating in mice and human NPY also increased food intake, whereas the free acid of NPY was inactive.
Abstract: Neuropeptide Y (NPY) stimulates eating in a number of species. In the studies reported here, intracerebroventricular administration of porcine NPY increased eating in mice. In the presence of food, NPY caused enhancement of water intake, whereas in the absence of food, NPY suppressed water intake. Behavioral analysis showed that NPY decreased the latency to eat, increased the time spent eating, and decreased grooming. Human NPY also increased food intake, whereas the free acid of NPY was inactive. Although some minor discrepancies in response were noted overall, NPY was as effective at stimulating food intake in genetically obese (ob/ob) mice compared with their lean littermates (ob/-), in genetically diabetic mice (db/db) and their nondiabetic heterozygote control (db/m), in streptozocin-induced diabetic mice and their controls, and in adult (8 mo old) compared with old (25 mo old) mice.
152Â citations
TL;DR: This topic remains controversial, with a considerable body of evidence suggesting that vasopressin is elevated during adrenal insufficiency not because of a loss of central steroid negative feedback but because of alterations in plasma volume osmolality (renal mechanisms).
Abstract: Several lines of evidence have suggested that neurohypophysial vasopressin secretion is under the influence of glucocorticoid negative feedback. Studies in clinical and experimental adrenal insufficiency have suggested that the impaired water excretion accompanying that syndrome may be due to elevated vasopressin levels. Furthermore, both the impaired water excretion and elevated vasopressin levels observed in adrenal insufficiency may be normalized by glucocorticoid treatment. This topic remains controversial, with a considerable body of evidence suggesting that vasopressin is elevated during adrenal insufficiency not because of a loss of central steroid negative feedback but because of alterations in plasma volume osmolality (renal mechanisms). Vasopressin responses to a variety of stimuli (hemorrhage, hypoxia, hypertonic saline) in normal humans and animals appear to be attenuated or eliminated by pretreatment with glucocorticoids. However, the vasopressinergic system appears to be considerably less sensitive to negative feedback than the corticotropin-releasing factor-adrenocorticotropic hormone (ACTH) system. There is evidence that the locus for this inhibitory effect is both directly at the posterior pituitary and within the hypothalamus. It is unlikely that corticosteroid negative feedback closes a direct hypothalamo-neurohypophysial-adrenocortical feedback loop. Since neurohypophysial vasopressin is involved in the control of ACTH secretion, it is more likely that the modulation of neurohypophysial vasopressin by glucocorticoid is an integral part of the overall negative-feedback control of ACTH secretion. The physiological role of glucocorticoid inhibition of vasopressin secretion remains speculative.
148Â citations
TL;DR: Dietary adjustments apparently influence the control of body temperature by the central nervous system, which results in a modification of the pattern of torpor in hibernating chipmunks.
Abstract: Membrane lipids of vertebrate animals that tolerate cold are high in polyunsaturated fatty acids. Because the lipid composition of cellular membranes in mammals can be experimentally altered by diet, we investigated whether a diet rich in polyunsaturated fatty acids would lengthen bouts of torpor and reduce the minimum body temperature in hibernating chipmunks (Eutamias amoenus) compared with a diet rich in saturated fatty acids. Animals on the highly unsaturated diet showed significantly longer bouts of torpor, lower minimum body temperatures, and lower metabolic rates than those on a saturated diet. Animals on a control diet were intermediate. These dietary adjustments apparently influence the control of body temperature by the central nervous system, which results in a modification of the pattern of torpor. The observations also suggest a role of nutritional ecology in hibernation.
142Â citations
TL;DR: The first microprocessor-controlled monitors for collection of data on depth, heart rate, and body temperature of one fetal and five adult male freely swimming Weddell seals are developed and successfully used.
Abstract: We have developed and successfully used the first microprocessor-controlled monitors for collection of data on depth, heart rate, and body temperature of one fetal and five adult male freely swimming Weddell seals. Adult seals almost invariably experienced a prompt bradycardia at the start of each dive, and the mean heart rate during diving was significantly lower for dives greater than 20 min (P greater than 0.999). The heart rate was also significantly greater during the ascent portion of dives when compared with the descent portion (P greater than 0.95). The fetal seal experienced a slow onset of bradycardia when its mother dived; during diving the fetal heart rate decreased by an average of 1.1 beats/min for each minute of the dive. The fetal heart rate generally took approximately 10 min to recover to predive levels after its mother resurfaced to breathe. The body temperature of one adult male Weddell seal showed a decrease of greater than 1.5 degrees C from resting levels before dives of greater than 15 min were initiated and a drop of over 2 degrees C before dives of greater than 30 min duration.
TL;DR: Regional cerebral blood flow was studied in the cat by the intravenous injection of the tracer [14C]iodoantipyrine and subsequent regional brain dissection and may represent the result of metabolic activation of sensory cortex.
Abstract: Regional cerebral blood flow was studied in the cat, with and without trigeminal ganglion stimulation, by the intravenous injection of the tracer [14C]iodoantipyrine and subsequent regional brain dissection. Electrical activation of the trigeminal ganglion led to a selective increase in regional blood flow in the frontal and parietal cortex that was bilateral without change in the posterior cortex, deep cerebral nuclei, white matter, or brain stem. Unilateral intracranial section of the facial nerve blocked the response in the ipsilateral frontal and parietal cortex, whereas bilateral facial nerve section blocked the contralateral frontal cortical response. The contralateral parietal cortical increase in blood flow was not affected by facial nerve section and may thus represent the result of metabolic activation of sensory cortex.
TL;DR: O2 consumption was measured in tissue slices of liver, kidney, and brain from Amphibolurus vitticeps and Rattus norvegicus both in the presence and absence of ouabain and it is postulated that this is a general difference between the cells of ectotherms and endotherm and thus partly explains the much higher levels of metabolism found in endothermic mammals.
Abstract: O2 consumption was measured at 37 degrees C in tissue slices of liver, kidney, and brain from Amphibolurus vitticeps and Rattus norvegicus (a reptile and mammal with same weight and body temperature) both in the presence and absence of ouabain. O2 consumption of the mammalian tissues was two to four times that of the reptilian tissues and the mammalian tissues used three to six times the energy for Na+-K+ transport than the reptilian tissues. Passive permeability to 42K+ was measured at 37 degrees C in liver and kidney slices, and passive permeability to 22Na+ was measured at 37 degrees C in isolated and cultured liver cells from each species. The mammalian cell membrane was severalfold "leakier" to both these ions than was the reptilian cell membrane, and thus the membrane pumps must use more energy to maintain the transmembrane ion gradients. It is postulated that this is a general difference between the cells of ectotherms and endotherms and thus partly explains the much higher levels of metabolism found in endothermic mammals.
TL;DR: The results suggest that IL 1 causes hypoglycemia by increasing insulin blood levels and probably also by mechanisms independent of the insulin secretagogue action of this cytokine.
Abstract: Alterations in glucose metabolism are known to occur during certain types of inflammation and infectious diseases. Interleukin 1 (IL 1), an immune-derived cytokine released during these processes, is proposed to function as a mediator of such alterations, since administration of low subpyrogenic doses of human rIL 1 to mice and rats produced hypoglycemia. In mice this effect was paralleled by increased insulin, glucagon, and corticosterone blood levels. When IL 1 was repeatedly injected, mice remained hypoglycemic for at least 14 h after the last injection. Furthermore, these animals responded normally to a challenge with glucose, thus suggesting that the proper function of the pancreas was preserved. A moderate hypoglycemia, paralleled by increased glucagon and corticosterone blood levels, was also observed in IL 1-injected rats, but no increase in insulin levels was detected. IL 1 administration to adrenalectomized rats resulted in a more marked hypoglycemia and in a profound hypoinsulinemia. The results suggest that IL 1 causes hypoglycemia by increasing insulin blood levels and probably also by mechanisms independent of the insulin secretagogue action of this cytokine.
TL;DR: The hypothesis that the OVLT contains osmoreceptors involved in physiological responses to cellular dehydration is supported and involvement in drinking and secretion of AVP in response to ANG II is suggested.
Abstract: We have proposed that the organum vasculosum laminae terminalis (OVLT) contains osmoreceptors involved in the regulation of drinking and secretion of arginine vasopressin (AVP) in the dog. By use of the technique of electrolytic ablation, conscious dogs were evaluated for their responses to acute peripheral challenges of hypertonic NaCl and angiotensin II (ANG II) and hemorrhage (20 ml/kg) before and after destruction of the OVLT (n = 7) or adjacent tissue (n = 9) as a control. Lesions confined to the tip of the optic recess and destroying greater than 90% of the OVLT caused a dramatic increase in the threshold to drink and increase plasma AVP levels and a significant (P less than 0.01) reduction in the magnitude of these responses to an osmotic stimulus. Drinking and secretion of AVP in response to ANG II, but not the rise in peripheral corticosteroids, were also blocked (P less than 0.01) by ablation of the OVLT. In contrast responses to hemorrhage were not affected by the lesion. These results support the hypothesis that the OVLT contains osmoreceptors involved in physiological responses to cellular dehydration and suggest involvement in drinking and secretion of AVP in response to ANG II. The results also indicate that forebrain mechanisms which depend on the OVLT are independent of mechanisms responding to hemorrhage in conscious dogs.
TL;DR: The correlation of glial alkalinization with evoked electrical activity suggests that modulation of intracellular pH of glia may have important functional implications and the observation that glia initially become more alkaline during electrical activity is paradoxical.
Abstract: Modulation of intracellular pH is widely implicated in the control of cell growth and metabolism, yet little is known about intracellular pH and brain function. To determine how stimulation of brain may affect the intracellular pH of mammalian glial cells, rat cortical astrocytes were studied for the first time in vivo using pH-sensitive electrodes of submicron caliber. Stimulation of the cortical surface caused a cytoplasmic alkaline shift of tenths of a pH within seconds. Cessation of induced electrical activity was followed by pH recovery and a small acid rebound. Recordings obtained during cortical-spreading depression revealed similar but generally larger intracellular pH shifts. Production of metabolic acids is known to occur when the brain is stimulated and has led to the long-held presumption that brain cells accordingly become more acidic. The observation that glia initially become more alkaline during electrical activity is thus paradoxical. The correlation of glial alkalinization with evoked electrical activity suggests that modulation of intracellular pH of glia may have important functional implications.
TL;DR: The data support the notion that apoeccrine glands develop during puberty in the axillae from eccrine or eccrinelike sweat glands.
Abstract: Evidence is presented that in adult human axillae there exists a third type of sweat gland tentatively designated as the apoeccrine sweat gland. This type of gland shows a segmental or diffuse apocrinelike dilatation of its secretory tubule but has a long and thin duct which does not open into a hair follicle. The electron microscopy of its dilated segment is often indistinguishable from that of the classical apocrine gland. The less remarkably dilated segment of the apoeccrine gland tends to retain intercellular canaliculi and/or dark cells. These apoeccrine glands are consistently present in adult human axillae regardless of sex or race. In the axillae of the two 6-yr-old subjects, both classical apocrine and eccrine glands were present but no apoeccrine glands were found. Between 8-14 yr of age, the number of large eccrine glands with or without partial segmental dilatation gradually increased. At 16-18 yr of age, the number of apoeccrine glands increased to as high as 45% of the total axillary glands. The data support the notion that apoeccrine glands develop during puberty in the axillae from eccrine or eccrinelike sweat glands.
TL;DR: The results emphasize the importance of SE neurons and surrounding area in integrating the brain vasomotor output to spinal preganglionic neurons.
Abstract: Lumbar sympathetic nerve discharge and unit activity of reticulospinal sympathoexcitatory (SE) neurons located in nucleus paragigantocellularis lateralis (PGCL) were recorded in rats. The sympathoinhibition produced by low-frequency stimulation of vagal afferents was abolished by bilateral microinjections of 20 pmol of bicuculline methiodide (BIC, a GABA-receptor antagonist) into PGCL and was converted into a pressor response by injections of 100 pmol. These BIC injections also inhibited the arterial baroreflex in a dose-dependent manner. In contrast the sympathoexcitation produced by high-frequency stimulation of vagal afferents was selectively blocked by bilateral injections of kynurenic acid (KYN, a Glu-receptor antagonist) into PGCL. Convergence of vagal excitatory, vagal inhibitory, and arterial baroreceptor inputs was detected in all SE neurons recorded. Single-pulse stimulation of vagal afferents produced up to two peaks of excitation of SE neurons, both blocked by iontophoretic applications of KYN and at least one inhibitory period selectively blocked by iontophoresis of BIC. The results emphasize the importance of SE neurons and surrounding area in integrating the brain vasomotor output to spinal preganglionic neurons.
TL;DR: Physiological experiments for validation and observations on the use of the method with 243 rats indicate that the protocol described can assess total as well as at least 11 different types of selective subdiaphragmatic vagotomies, including surgeries for which no assays have existed.
Abstract: A new protocol that provides a sensitive, reliable, and practical test for completeness of selective as well as total subdiaphragmatic vagotomies is described. This protocol employs a microscopic inventory of retrogradely labeled neurons in topographically distinct regions of the dorsal motor nucleus to determine which vagal branches have been surgically destroyed. Physiological experiments for validation and observations on the use of the method with 243 rats indicate that the protocol described can assess total as well as at least 11 different types of selective subdiaphragmatic vagotomies, including surgeries for which no assays have existed. Furthermore, the technique can identify cases where a branch is only partially destroyed. Other strengths include the facts that the protocol provides a simultaneous inventory of the different branches in a single test, is not influenced by the general health of the animal, and does not interfere with concurrent behavioral or physiological tests. Limitations include the facts that the tracer inventory requires a minimal survival period, can only be done postmortem, and has low resolution for cuts of the vagal hepatic branch. Aspects of the protocol critical to its implementation, including specifics for using the fluorescent tracer true blue, are discussed. Other tracers with similar diffusion characteristics, such as fluoro-gold and fast blue, can be used with equal effectiveness with this protocol.
TL;DR: Regulation of caloric intake, pancreatic sympathetic tone, and plasma insulin levels were three important differences between rats that resisted and those that developed DIO on high-energy diets.
Abstract: After 15 wk on a moderately high-calorie high-fat (CM) diet, 43% of 40 3-mo-old male Sprague-Dawley rats developed diet-induced obesity (DIO) (29% more weight gain), whereas 57% of diet-resistant (DR) rats gained no more weight than 20 chow-fed controls. When switched to chow for another 7 wk, DR rats ate 13% less, gained 55% less weight, and had 49% lower food efficiency, whereas DIO rats ate 4% less but had comparable weight gain and efficiency to controls. DIO rats had 29% more carcass lipid (percent of carcass weight). DIO rat retroperitoneal white adipose pads had 65% more cells that were the same size as those in chow-fed pads; DR rat cells were similar to controls. Both DR and DIO rats increased norepinephrine turnover in their interscapular brown adipose pads by greater than 90%. DIO rats also had 40% lower pancreatic turnover; their plasma insulin levels were 327% of controls after 15 wk on the CM diet and 188% after 7 wk on chow. DR levels were the same as controls at both times. Therefore, regulation of caloric intake, pancreatic sympathetic tone, and plasma insulin levels were three important differences between rats that resisted and those that developed DIO on high-energy diets.
TL;DR: The study evaluated the hypothesis that during exercise autonomic neuroendocrine activity and, in turn, substrate mobilization, is subjected to feed-forward stimulation from motor centers, and hormonal responses were similar in the two experiments.
Abstract: The study evaluated the hypothesis that during exercise autonomic neuroendocrine activity and, in turn, substrate mobilization, is subjected to feed-forward stimulation from motor centers. Eight young healthy men bicycled for two 20-min periods without (control, C) as well as during partial neuromuscular blockade with tubocurarine (Cu). 3-[3H]glucose was infused, and arterialized hand vein blood was sampled. In period 1 O2 consumption (VO2) (56% VO2 max), heart rate, and blood lactate were identical in Cu compared with C experiments, whereas hand grip strength was lower and perceived exertion [14.0 +/- 1.5 vs. 9.1 +/- 1.2 (SE) points, P less than 0.01] higher in Cu experiments, indicating higher motor center activity. Concentrations of norepinephrine [7.39 +/- 1.18 (Cu) vs. 5.14 +/- 1.06 (C) nmol/l], epinephrine (1.69 +/- 0.33 vs 0.87 +/- 0.16 nmol/l), growth hormone (25.9 +/- 7.3 vs. 11.5 +/- 4.7 mU/l), and adrenocorticotropin hormone (11.3 +/- 1.3 vs. 5.5 +/- 0.7 pmol/l) attained higher values in Cu than in C experiments (P less than 0.05). The initial increase in glucose production was enhanced in Cu (8.1 +/- 1.6 mumol.min-1.kg-1) compared with C experiments (3.9 +/- 1.9, P less than 0.05), and plasma glucose only increased in Cu experiments. Free fatty acid (P less than 0.05) and glycerol (P less than 0.1) concentrations were higher in Cu than in C experiments. In period 2 identical perceived exertion was achieved in the two experiments by reducing work load in Cu experiments. In this period hormonal responses were similar in the two experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The presumption that sensory information does not arise from white adipose tissue was reevaluated using the neuroanatomical tracer, "true blue" using rats after tracer was implanted into inguinal or dorsal subcutaneous fat depots.
Abstract: The presumption that sensory information does not arise from white adipose tissue was reevaluated using the neuroanatomical tracer, "true blue." Fluorescent cell bodies were observed in dorsal root ganglia of rats after tracer was implanted into inguinal or dorsal subcutaneous fat depots. Sensory information from adipose tissue may play an important role in the regulation of regional and total body fat mass.
TL;DR: The significant neurohypophysial hormone secretion in response to both nausea-producing agents and CCK suggests that AVP secretion in monkeys, similar to OT secretion in rats, might reflect activation of central pathways mediating nausea and/or inhibition of food intake, even when overt illness is not produced.
Abstract: Administration of lithium chloride and copper sulfate to adult monkeys caused marked elevations in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. Emesis was produced in five of the seven animals given these agents, in support of nausea as the main stimulus to AVP release. A similar pattern of AVP release without OT release was found after administration of cholecystokinin (CCK). Although most monkeys vomited in response to 10 micrograms/kg of CCK, a significant increase in plasma AVP levels also was produced with a dose of 1 microgram/kg, which did not produce emesis in any animal. These findings are in marked contrast with previous results in rats, which indicated that lithium chloride, copper sulfate, and CCK each stimulated OT rather than AVP release. Despite this interspecies difference, the significant neurohypophysial hormone secretion in response to both nausea-producing agents and CCK suggests that AVP secretion in monkeys, similar to OT secretion in rats, might reflect activation of central pathways mediating nausea and/or inhibition of food intake, even when overt illness is not produced.
TL;DR: The results may be interpreted to indicate either that cell bodies responsible for changes in cardiovascular variables during electrical stimulation are not located in the amygdala or that chemical and electrical stimulation affect different neuronal elements in circuits Located in the same anatomic site.
Abstract: Electrical stimulation of the amygdala has been shown to produce changes in cardiovascular variables. To locate neuronal cell bodies responsible for these changes, responses of arterial pressure (AP) and heart rate (HR) to DL-homocysteate (DLH, 0.15 M, 50-100 nl) microinjected into sites in three amygdaloid nuclei were compared with responses to electrical (90-150 microA) stimulation of the same sites in 35 artificially ventilated, paralyzed, urethan-anesthetized rats. Electrical stimulation resulted in depressor responses in most sites (89%). Changes in AP were accompanied by variable changes in HR. Chemical stimulation produced significantly fewer (25%) depressor responses. Similar results were obtained with injections of 1.0 M DLH. To eliminate the influence of the anesthetic on these responses, AP was recorded in nine conscious rats while stimulating the amygdala. Changes in behavior and AP in these animals could be obtained only by electrical stimulation. These results may be interpreted to indicate either that cell bodies responsible for changes in cardiovascular variables during electrical stimulation are not located in the amygdala or that chemical and electrical stimulation affect different neuronal elements in circuits located in the same anatomic site.
TL;DR: The ToBEC used under the conditions defined in this study accurately predicted the FFM and TBW content of infant miniature pigs and will be applicable to the interpretation of the TOBEC measurements of human infants provided their FFM is of comparable shape to that of the piglets.
Abstract: This study used an animal model to analyze the effect of body geometry and chemical composition on the calibration of a total body electrical conductivity (TOBEC) instrument developed to measure the body composition of human infants. The TOBEC signal (adjusted for length) of infant miniature pigs from 10 to 33 days of age correlated highly with their chemically analyzed fat-free mass (FFM; r = 0.998) and total body water contents (TBW; r = 0.998); 95% prediction intervals (approximately +/- 2 SEE) for individual measurements were +/- 0.16 kg FFM and +/- 0.12 liter water. These values were significantly improved (+/- 0.08 kg and +/- 0.06 liter, respectively) by accounting for individual variability in weight/length2. The effect of variations in the composition of FFM on the TOBEC measurements was evaluated by comparing the response of the infant piglets with that of adult rabbits of similar size. The differences in composition, primarily TBW and Na content, were insufficient to alter the electrical properties of FFM appreciably. Thus the TOBEC used under the conditions defined in this study accurately predicted the FFM and TBW content of infant miniature pigs. The calibration derived from the piglets will be applicable to the interpretation of the TOBEC measurements of human infants provided their FFM is of comparable shape to that of the piglets. Differences in composition are likely to be of consequence only if the proportion of fat within the FFM and the FFM density are widely divergent. This, however, does not appear to be the case.
TL;DR: It is concluded that hamsters show the expected physiological, pharmacological, and biochemical signs of cold acclimation (i.e., an increased capacity for nonshivering thermogenesis).
Abstract: To investigate the acclimation process in a hibernator, four different parameters of thermogenin amount and activity were investigated in brown adipose tissue mitochondria from cold-exposed and cold-acclimated Syrian hamsters. Hamsters, which are hibernators, have been considered to be "primed" for thermogenesis and thus not to show cold-acclimation effects, but here a significant increase in [3H]GDP-binding capacity was observed (from 0.5 nmol in control to 0.9 nmol GDP/mg in cold-acclimated hamsters), and this increase was paralleled by an increase in thermogenin antigen amount, as measured in an enzyme-linked immunosorbent assay. The transient nature of the effect of cold exposure on [3H]GDP binding, characteristically observed with rat mitochondria, was not observed with hamster mitochondria, and the increase in [3H]GDP binding occurred without a change in the dissociation constant (0.7 microM). The increase in thermogenin amount was paralleled by an increase both in GDP-sensitive Cl- permeability of the mitochondria and in GDP-sensitive respiration. It was established that it is the maximal activity of thermogenin that is rate limiting for thermogenesis in isolated mitochondria, provided that an optimal substrate is used (such as palmitoyl carnitine). Cold acclimation also increased the total amount of mitochondria in the tissue, leading totally to a sixfold increase in thermogenin content of the hamster. It is concluded that (contrary to the general view) hamsters show the expected physiological, pharmacological, and biochemical signs of cold acclimation (i.e., an increased capacity for nonshivering thermogenesis).
TL;DR: Serum levels of IL 1 and TNF were evaluated in mice with a tumor, sterile inflammation, endotoxinemia, or generalized peritonitis and suggest that a hepatic acute-phase protein response can occur during inflammatory states without the appearance of either IL 1 or TNF in the circulation.
Abstract: It is proposed that interleukin 1 (IL 1) and tumor necrosis factor (TNF) alpha play central roles in the host's response to inflammation. Yet circulating concentrations have not been frequently measured in many inflammatory states. Serum levels of IL 1 and TNF were evaluated in mice with a tumor, sterile inflammation, endotoxinemia, or generalized peritonitis where an acute-phase protein response was documented. In tumor-bearing mice, no IL 1 or TNF could be detected despite marked increases in the serum concentration of the acute-phase reactant protein, amyloid P. In mice with peritonitis, induced by cecal ligation and perforation, or a turpentine-induced subcutaneous abscess, IL 1 but not TNF could be detected in the serum. Only expansion of the reticuloendothelial system with Corynebacterium parvum and subsequent challenge with endotoxin resulted in serum TNF appearance. The failure to observe IL 1 or TNF in any of the disorders could not be explained by inhibitors. Rather, the data suggest that a hepatic acute-phase protein response can occur during inflammatory states without the appearance of either IL 1 or TNF in the circulation. Circulating levels of both monokines do not appear to be a universal finding in inflammation.
TL;DR: Results of this study indicate that CRF acts within the central nervous system to increase plasma glucose and glucagon concentrations, mean arterial pressure, and heart rate by activation of the autonomic nervous system.
Abstract: Corticotropin-releasing factor (CRF) is thought to be an endogenous mediator of adrenocorticotropic hormone release following stress. We examined if CRF initiates further biological actions that are observed in response to stressful events. Male beagle dogs (10-12 kg) were fitted with a chronic intracerebroventricular cannula, intra-arterial and intravenous catheters, as well as a gastric fistula. Synthetic human CRF was microinjected into the third cerebral ventricle in conscious animals. CRF (0.1-1.0 nmol/kg) significantly (P less than 0.01) increased plasma concentrations of epinephrine, norepinephrine, glucagon, and glucose and elevated mean arterial pressure and heart rate. Pretreatment of the animals with the ganglionic blocking agent chlorisondamine completely abolished the increases in plasma catecholamine and glucose concentrations as well as the elevations in blood pressure and heart rate. CRF significantly (P less than 0.01) inhibited gastric acid secretion, but not plasma gastrin concentrations stimulated by an 8% liquid peptone meal. The gastric inhibitory action of CRF was completely prevented by chlorisondamine and, in part, by naloxone and a vasopressin antagonist. In contrast, bilateral truncal vagotomy did not affect the gastric inhibitory action of CRF. The results of this study indicate that CRF acts within the central nervous system to increase plasma glucose and glucagon concentrations, mean arterial pressure, and heart rate by activation of the autonomic nervous system. CRF inhibits meal-stimulated gastric acid secretion by activation of the sympathetic nervous system and, in part, by opiate and vasopressin-dependent pathways and not by inhibition of gastrin release.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Increased renal sympathetic nerve activity, but not angiotensin II, mediates the blunted diuretic and natriurtic responses to atrial natriuretic peptide in conscious cirrhotic rats.
Abstract: The diuretic and natriuretic responses to atrial natriuretic peptide in conscious rats with cirrhosis (chronic bile duct ligation) were examined. Cirrhotic rats had sodium retention, ascites, and elevated liver weights. In conscious control rats, atrial natriuretic peptide increased urine flow rate and urinary sodium excretion. In conscious cirrhotic rats, atrial natriuretic peptide had no effect on urine flow rate or urinary sodium excretion. Renal denervation reversed the blunted diuretic and natriuretic responses to atrial natriuretic peptide in cirrhotic rats. Renal sympathetic nerve activity increased in conscious cirrhotic rats during infusion of atrial natriuretic peptide but decreased in conscious control rats. Inhibition of the renin-angiotensin system with captopril had no effect on the diuretic or natriuretic responses to atrial natriuretic peptide in conscious control or cirrhotic rats. Mean arterial pressure, glomerular filtration rate, and renal plasma flow were affected similarly by atrial natriuretic peptide in control and cirrhotic rats. Increased renal sympathetic nerve activity, but not angiotensin II, mediates the blunted diuretic and natriuretic responses to atrial natriuretic peptide in conscious cirrhotic rats.
TL;DR: These findings contrast with the view that most heat transfer occurs in the capillaries and suggest that vascular heat transfer analysis must take into account the vascular architecture of the 50- to 1,000-micron vessels where mostHeat transfer occurs.
Abstract: This study was undertaken to gain a better understanding of the fundamental mechanisms of micro- and macrovascular heat transfer by experimentally identifying those vessels most important in the process. Tissue temperature fields around thermally nonequilibrated vessels were determined using a small temperature sensor that was guided through the rabbit thigh to generate a detailed temperature map. The measurements revealed that the lower limit of vessel size for thermal nonequilibration was 100 microns for arteries and 400 microns for veins. Local temperature fields were found around four of the five (80%) arteries that were greater than 300 microns in diameter but in only 3 of the 12 (25%) veins greater than 400 microns. These experimental results are in good agreement with previously published theoretical studies (5) in which it was concluded that thermal equilibration in the branching countercurrent vascular network of the rabbit limb occurs in vessels an order of magnitude larger than the capillaries. In those studies the smallest vessels capable of carrying heat were predicted to be 50 microns ID with the major blood tissue heat exchange occurring in vessels greater than 100 micron ID. These findings contrast with the view that most heat transfer occurs in the capillaries and suggest that vascular heat transfer analysis must take into account the vascular architecture of the 50- to 1,000-micron vessels where most heat transfer occurs.