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At least 307 records · Page 17Linked to original sources
PubMed2005

Energy expenditure by intravenous administration of glucagon-like peptide-1 mediated by the lower brainstem and sympathoadrenal system.

Glucagon-like peptide-1 (GLP-1) is released from the gut in response to nutrient ingestion. Intravenous (iv) administration of GLP-1 (50 pmol-20 nmol) elicited dose-dependent increases in the rate of whole-body O2 consumption (VO2), an index of energy expenditure, and heart rate of urethane-anesthetized rats. The body core (colonic) temperature increased up to 0.3 degrees C without accompanying alteration of tail skin temperature. Intracerebroventricular (icv) administration of GLP-1 induced a slower and smaller increase in VO2 than the intravenous administration. The injection of glucagon-like peptide-2 (iv or icv) had no effect on VO2, body temperatures, or heart rate. Decerebration had no effect on the thermogenic responses induced by the iv administration of GLP-1, suggesting that the forebrain is not essential for these responses. However, cervical spinal transection greatly attenuated the responses, suggesting the critical involvement of the lower brainstem. Adrenalectomy or pretreatment with an autonomic ganglion blocker, hexamethonium, or a beta-adrenergic blocker, propranolol, also significantly attenuated the thermogenic response. However, subdiaphragmatic vagotomy or celiac-superior mesenteric ganglionectomy had no effect. Rats made insulin-deficient by pretreatment with streptozotocin also exhibited the normal thermogenic response to GLP-1. These results suggest the involvement of the GLP-1 in postprandial energy expenditure, mediated by the lower brainstem and sympathoadrenal system.

Adrenal Glands↗
PubMed2002

Central urocortin activation of sympathetic-regulated energy metabolism in Wistar rats.

The corticotropin-releasing hormone (CRH) system, including CRH and urocortin (UCN), is implicated in the central control of appetite and energy metabolism. Urocortin, a recently isolated neuropeptide closely related to CRH is involved in the central signaling cascade that inhibits energy intake. When administered intracerebroventricularly and intra-hypothalamically, UCN potently decreases food intake. Receptors for UCN, while widely distributed, are expressed in hypothalamic nuclei. As the hypothalamus is involved in modulating autonomic outflow, UCN may also act as a catabolic neuropeptide to facilitate energy expenditure through sympathetic-regulated thermogenesis. To test the hypothesis that UCN also enhances regulatory energy expenditure via the activation of the sympathetic nervous system, we examined whole body oxygen consumption (VO(2)) and colonic temperature in male Wistar rats in response to central UCN administration. That is, the intracerebroventricular injection of 1.0 microg of UCN in male Wistar rats (n=10) significantly increased whole body oxygen consumption compared to PBS control. In addition, colonic temperature was significantly increased (Delta0.7 +/- 0.08 degrees C) in UCN- vs. PBS-administered rats, which was prevented by pretreatment with the ganglionic blocker chlorisondamine. These studies suggest that UCN acutely increased whole body oxygen consumption and body temperature via central activation of sympathetic outflow.

Animals↗
PubMed1999

Involvement of sympathetic activation and brown adipose tissue in calcitonin gene-related peptide-induced heat production in the rat.

We previously reported that microinjection of calcitonin gene-related peptide (CGRP; 1.6-8.0 pmol, 0.2-1.0 microliter) into the ventromedial hypothalamus (VMH) increased oxygen consumption (VO(2)), heart rate (HR), colonic temperature (T(co)), and temperature of interscapular brown adipose tissue (T(IBAT)). In the present study, we investigated whether the autonomic nervous system is involved in the CGRP-induced heat production in urethane-anesthetized rats. Intraperitoneal administration of the ganglion blocker hexamethonium (20 mg/kg) or the beta-adrenergic antagonist propranolol (5 mg/kg) suppressed the CGRP-induced increases in VO(2), HR, T(co), and T(IBAT). Pretreatment with the alpha-adrenergic antagonist phentolamine (5 mg/kg) partly attenuated the heat production response but did not affect the tachycardiac response. Bilateral sectioning of the nerves supplying the IBAT attenuated the CGRP-induced increase in T(IBAT) but not significantly that in VO(2) or T(co). In rats with adrenal demedullation, the effects of CGRP were similar to those in intact rats. These results suggest that the CGRP-induced heat production is mediated by the sympathetic nervous system and, at least in part, by the BAT through the alpha- and beta-adrenoceptors.

Adipose Tissue, Brown↗
PubMed2002

Intestinal ischemia preconditions myocardium: role of protein kinase C and mitochondrial K(ATP) channel.

OBJECTIVE: The present study was designed to test the hypothesis that intestinal ischemia results in an early preconditioning against myocardial infarction and that the mechanism of the early preconditioning involves the activation of protein kinase C-mitochondrial K(ATP) channel signaling pathway in anesthetized rats. METHODS: Rats were either preconditioned with a 25-min occlusion of the superior mesenteric artery followed by 15 min of reperfusion or underwent a 40-min sham period. Subsequently, all rats were subjected to a sustained 30 min of coronary occlusion and 180 min of reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining. RESULTS: In sham-operated rats receiving no pharmacological intervention, the percentage of myocardial infarct within the area at risk and left ventricle was 73+/-4% and 31+/-2%, respectively, and these were significantly reduced to 44+/-4% and 23+/-1% (P<0.01) after intestinal ischemia preconditioning. Intravenous injection of protein kinase C inhibitors chelerythrine (5 mg/kg) and staurosporine (50 microg/kg) or a specific mitochondrial K(ATP) channel inhibitor 5-hydroxydecanoate (5 mg/kg) 5 min before sustained myocardial ischemia abolished the preconditioning afforded by intestinal ischemia. However, hexamethonium, a ganglion blocker, did not attenuate the preconditioning. CONCLUSIONS: These data provide pharmacological evidence that protein kinase C and mitochondrial K(ATP) channel are involved in the mechanism of the early preconditioning induced by intestinal ischemia.

Alkaloids↗
PubMed1999

Cardiac transplantation does not effect ischaemia-induced arrhythmias in rats.

OBJECTIVE: In many species arrhythmias induced by myocardial ischaemia appear to be in part dependent upon cardiac sympathetic nerves. However, previous experiments in rats did not suggest that myocardial or other catecholamines are involved in ischaemic arrhythmogenesis in this species. The aim of this study was to investigate this further using transplanted hearts. METHODS: We transplanted 'donated' hearts onto the abdominal aorta of recipient rats and, at varying periods after transplantation, subjected donated and recipient hearts to occlusion of the left anterior descending (LAD) coronary artery. Donated and recipient hearts were tested at various times after transplantation for responsiveness to drugs acting upon aspects of the autonomic nervous system. The intention of this latter study was to assess the status of innervation and receptors simultaneously in both donated and recipient hearts. RESULTS: Donated (transplanted) hearts showed responses consistent with denervation and receptor supersensitivity. Changes varied with the duration of the transplant. Over the same period recipient hearts did not change in responsiveness to drugs. When subjected to coronary artery occlusion, transplanted hearts responded to occlusion with the same frequency and severity of arrhythmias as recipient and other control hearts, regardless of the duration of transplant, or sensitivity to drugs. CONCLUSIONS: The results of these experiments suggest that cardiac innervation is not an important factor in the genesis of ischaemia-induced arrhythmias in rats.

Acetylcholine↗
PubMed1998

Autonomic mechanisms in the acute cardiovascular effects of cocaine in conscious rats.

We studied the differential involvement of central dopaminergic activation and autonomic nervous system regulatory mechanisms in the cardiovascular responses to cocaine in conscious rats. Sprague-Dawley rats, Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were instrumented with catheters in the jugular vein and abdominal aorta at least 5 days before the experiment. Intravenous administration of cocaine (0.1-3.0 mg/kg) caused a dose-dependent increase in blood pressure that was biphasic, with a large and rapid increase peaking at 10 s, followed by a mild sustained pressor response. Pressor responses to cocaine were significantly greater in SHR when compared to WKY rats. However, pretreatment with dopamine D1 receptor antagonist SCH 23390 or the D2 receptor antagonist raclopride did not influence the effects of cocaine. Pretreatment with the alpha-adrenoceptor antagonist phentolamine or the ganglion blocker pentolinium blocked the peak response and reversed the more sustained response into a depressor effect. While pretreatment with propranolol alone did not alter the responses to cocaine, in rats pretreated with phentolamine and propranolol neither a pressor response nor a depressor response was observed. In conclusion, cocaine administration caused marked, but short lasting pressor responses that were mediated by sympathetic activation and alpha-adrenoceptor vasoconstriction with little involvement of central dopaminergic mechanisms. The rapid return of blood pressure towards baseline may be mediated by sympathoinhibition and beta-adrenoceptor-mediated vasodilatation, the latter of which being particularly prominent when alpha-adrenoceptor activation was prevented.

Acute-Phase Reaction↗
PubMed1999

Hemodynamic actions of systemically injected pituitary adenylate cyclase activating polypeptide-27 in the rat.

The aims of this study were (1) to characterize the hemodynamic mechanisms underlying the hypotensive effects of pituitary adenylate cyclase activating polypeptide-27 (PACAP-27 0.1-2.0 nmol/kg, i.v.) in pentobarbital-anesthetized rats, and (2) to determine the roles of the autonomic nervous system, adrenal catecholamines and endothelium-derived nitric oxide (NO) in the expression of PACAP-27-mediated effects on hemodynamic function. PACAP-27 produced dose-dependent decreases in mean arterial blood pressure and hindquarter and mesenteric vascular resistances in saline-treated rats. PACAP-27 also produced pronounced falls in mean arterial blood pressure in rats treated with the ganglion blocker, chlorisondamine (5 mg/kg, i.v.). The hypotensive and vasodilator actions of PACAP-27 were not attenuated by the beta-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.), or the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME 50 micromol/kg, i.v.). PACAP-27 produced dose-dependent increases in heart rate whereas the hypotensive response produced by the nitrovasodilator, sodium nitroprusside (10 microg/kg, i.v.), was associated with a minimal tachycardia. The PACAP-27-induced tachycardia was unaffected by chlorisondamine, but was virtually abolished by propranolol. These results suggest that the vasodilator effects of PACAP-27 are due to actions in the microcirculation rather than to the release of adrenal catecholamines and that this vasodilation may not involve the release of endothelium-derived NO. These results also suggest that PACAP-27 produces tachycardia by directly releasing norepinephrine from cardiac sympathetic nerve terminals rather than by direct or baroreceptor reflex-mediated increases in sympathetic nerve activity.

Anesthesia↗
PubMed2002

Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats.

PURPOSE: Adenosine triphosphate (ATP) (Sigma Chemical Co., St. Louis, Missouri) is known to contract animal as well as human detrusor muscle and recent investigations have shown an involvement of ligand gated purinergic-1 receptors in detrusor contraction. In addition, ligand gated purinergic-3 receptors have been demonstrated on suburothelial sensory nerves (C-fibers) and may be involved in distention induced initiation of the micturition reflex. We tested the hypothesis that ATP given intravesically can stimulate afferent nerves and initiate the micturition reflex. MATERIALS AND METHODS: Continuous cystometry was performed in conscious, freely moving, normal female Sprague-Dawley rats. Cystometric parameters were evaluated before and after drug administration. RESULTS: Instilled intravesically ATP (10 mM.) induced bladder overactivity in 6 animals with a mean increase in voiding pressure plus or minus standard error of 73 +/- 9 to 107 +/- 9 cm. water (p <0.01), mean baseline pressure increase of 5.32 +/- 0.58 to 12.71 +/- 1.01 cm. water (p <0.01) and mean bladder capacity decrease of 1.13 +/- 0.25 to 0.75 +/- 021 ml. (p <0.01). Lower concentrations had no significant effect. The effects of ATP were abolished by pretreatment with the ganglion blocker hexamethonium (40 mg./kg. ), nitric oxide synthase substrate L-arginine (Sigma Chemical Co.) (200 mg./kg. ) and neurokinin-2 receptor antagonist 123 (S)-N-methyl-N 123 4-(acetylamino-4-phenyl piperidone)-2-(3,4-dichlorophenyl) butyl 125 benzamide (Molecular Probes, Leiden, The Netherlands) (4 nmol.) given intravenously, the ligand gated purinergic-3 antagonist 2'-(or 3')-O-(trinitrophyl)adenosine 5'-triphosphate (50 microM./kg.) given intravenously and the k channel opener ZD6169 given intravesically.(ATP). CONCLUSIONS: ATP given intravesically can induce bladder overactivity, probably by stimulating suburothelial C-fibers. The data suggest that several mediators and mechanisms are involved in mechano-afferent transduction in the bladder.

Adenosine Triphosphate↗
PubMed1979

Guanethidine sulfate in the prevention of autonomic hyperreflexia.

Autonomic hyperreflexia constitutes the only medical emergency seen in spinal cord injury patients. Uncontrolled hypertension and bradycardia can result in seizures and death. The acute treatment of the syndrome has ranged from medical ganglionic blockers to topical anesthetic agents to surgical procedures. The oral use of 10 mg. guanethidine sulfate 3 times daily successfully prevented the major symptoms of the syndrome in 200 spinal cord injury patients with lesions above T5. Toxicity has been mild and the drug is recommended until the patients are voiding and are capable of self-care.

Autonomic Nervous System↗
PubMed2002

Involvement of the nitric oxide/L-arginine and sympathetic nervous systems on the vasodepressor action of human urotensin II in anesthetized rats.

This study examined if the nitric oxide (NO)/L-arginine pathway participates in and if the sympathetic nervous system attenuates the depressor action of human urotensin II. I.V. bolus injections of human urotensin II (0.1-30 nmol/kg) caused dose-dependent decreases in mean arterial pressure (MAP, EC(50) = 2.09 +/- 0.8 nmol/kg; Emax = -18 +/- 3 mmHg ) and increases in heart rate. The depressor response to human urotensin II (3 nmol/kg) was attenuated by approximately 50% in rats with MAP elevated through pretreatment with N(G)-nitro-L-arginine methyl ester (inhibitor of NO synthase), relative to that in rats with MAP elevated to a similar level through a continuous infusion of noradrenaline. Autonomic blockade with i.v. injections of mecamylamine (ganglion blocker) and propranolol (beta-adrenoceptor antagonist) markedly augmented the depressor response to human urotensin II, but almost completely attenuated the tachycardia. The results suggest that the depressor response to human urotensin II is partially mediated via the NO/L-arginine pathway, and is suppressed by activity of the sympathetic nervous system. Furthermore, tachycardic response to human urotensin II is primarily mediated indirectly via baroreflex mechanisms.

Adrenergic beta-Antagonists↗
PubMed2000

Nicotine-evoked [3H]5-hydroxytryptamine release from rat striatal synaptosomes.

The aim of this study was to characterize the pharmacology of presynaptic nicotinic cholinoceptors (nAChRs) that modulate release of 5-hydroxytryptamine (5-HT) from superfused rat brain synaptosomes preloaded with [3H]5-HT. Nicotine increased 5-HT release from striatal synaptosomes (maximally by 15-30%) but not from cerebral cortex or hippocampal synaptosomes. Release of striatal 5-HT was increased in a concentration-dependent manner by nicotine, epibatidine, cytisine, and ACh (with added esterase inhibitor and muscarinic antagonist). Respective EC50 values were: 0.5, 0.003, 0.1 and 0.7 microM. The maximal effect of each agonist was virtually completely blocked by a high concentration of the insurmountable nicotinic antagonist mecamylamine; at a higher concentration of epibatidine (3 microM), a mecamylamine-insensitive effect was revealed. Nicotine, ACh and epibatidine appeared equally efficacious, whereas cytisine was of lower efficacy (60-70% of ACh). Release evoked by a half-maximal concentration of nicotine was inhibited by the nicotinic antagonists dihydro-beta-erythroidine (IC50 0.04 microM) and methyllycaconitine (IC50 0.06 microM). Nicotine-evoked 5-HT release was not reduced by tetrodotoxin given in a concentration that blocked veratridine-evoked release. These findings provide functional evidence for a direct action of nicotine on 5-HT neurons in the brain. The presynaptic nAChRs that modulate striatal 5-HT release appear to possess a novel pharmacological profile.

4-Aminopyridine↗
PubMed2000

Mecamylamine blockade of both positive and negative effects of IV nicotine in human volunteers.

The ganglionic blocker mecamylamine blocks the positive reinforcing effects of IV nicotine, but has been shown to increase cigarette smoking behavior under some conditions. The effects of mecamylamine on subjective and physiologic responses to IV nicotine were evaluated in seven healthy male volunteer cigarette smokers who provided informed consent and resided on a clinical pharmacology research unit. On four separate days, each subject was given a different oral dose of mecamylamine (placebo, 5, 10, or 20 mg). One hour later subjects received the first of four doses of IV nicotine (placebo, 0.75, 1.5, and 3.0 mg); the remaining injections were given at 1-h intervals. Both the positive effects following 0.75 mg and negative effects following 3.0 mg of nicotine were significantly reversed by mecamylamine. Thus, the mecamylamine-induced increase in smoking may be due both to competitive blockade of nicotinic receptors and nicotine's reversal of aversive effects.

Adult↗
PubMed2002

Sympathetic activation by fenfluramine depletes brown adipose tissue norepinephrine content in rats.

The antiobesity agent fenfluramine (FEN) has been reported to produce an activation of sympathetic neurons to brown adipose tissue (BAT) resulting in thermogenesis. The present study was conducted to determine if FEN-induced activation of BAT is affected by the ambient temperature at which animals are maintained. Body temperature was determined in conscious male Sprague-Dawley rats using implanted temperature transmitters, and sympathetic activation of BAT was determined by measuring norepinephrine (NE) content. Animals maintained at 22 and 4 degrees C incurred a significant decline in core body temperature following FEN administration. FEN produced a significant depletion of BAT NE content, and the magnitude of BAT NE depletion was related to the dose of FEN (-57.4% at 3 mg/kg dose and -75.9% at 10 mg/kg dose). However, the extent of BAT NE depletion was equal at 22 and 4 degrees C. BAT NE depletion by FEN appears to depend on activation of sympathetic neurons because it was prevented by pretreatment with the ganglionic blocker pentolinium (10 mg/kg ip). Furthermore, NE depletion by FEN could be blocked with fluoxetine (10 mg/kg ip) pretreatment, indicating that the action of FEN is mediated through the release of serotonin.

Adipose Tissue↗
PubMedDate not supplied

Autonomic control of the venous system in health and disease: effects of drugs.

The venous system contains approximately 70% of the blood volume. The sympathetic nervous system is by far the most important vasopressor system in the control of venous capacitance. The baroreflex system responds to acute hypotension by concurrently increasing sympathetic tone to resistance, as well as capacitance vessels, to increase blood pressure and venous return, respectively. Studies in experimental animals have shown that interference of sympathetic activity by an alpha1- or alpha2-adrenoceptor antagonist or a ganglionic blocker reduces mean circulatory filling pressure and venous resistance and increases unstressed volume. An alpha1- or alpha2-adrenoceptor agonist, on the other hand, increases mean circulatory filling pressure and venous resistance and reduces unstressed volume. In humans, drugs that interfere with sympathetic tone can cause the pooling of blood in limb as well as splanchnic veins; the reduction of cardiac output; and orthostatic intolerance. Other perturbations that can cause postural hypotension include autonomic failure, as in dysautonomia, diabetes mellitus, and vasovagal syncope; increased venous compliance, as in hemodialysis; and reduced blood volume, as with space flight and prolonged bed rest. Several alpha-adrenoceptor agonists are used to increase venous return in orthostatic intolerance; however, there is insufficient data to show that these drugs are more efficacious than placebo. Clearly, more basic science and clinical studies are needed to increase our knowledge and understanding of the venous system.

Aging↗
PubMed2003

Microneurography in anesthetized rats for the measurement of sympathetic nerve activity in the sciatic nerve.

Microneurography is widely used for the measurement of human peripheral sympathetic nerve activity (SNA) in conscious subjects by virtue of its low invasive nature, but has rarely been employed in animal experiments. Because the low invasive nature sometimes is very useful even in animal experiments, we tested its feasibility for the measurement of SNA in the sciatic nerve of the anesthetized rat, aiming in particular to establish a methodology for measurement. A tungsten microelectrode was inserted into the nerve exposed at the thigh level to detect the "spontaneous, intermittent burst" signal that is one of the main characteristics of compound SNA. Such signals were found in more than 70% of experiments after surgical operators became accustomed to the method. Whenever such signals were detected, electrical stimulation of the sympathetic chain resulted in induced action potentials detected with the microelectrode after a reasonable conduction period. The spikes were successfully reduced after administration of hexamethonium bromide, a sympathetic ganglion blocker. On the other hand, induced spikes were never observed when we failed to find the "spontaneous, intermittent burst" signal. The results demonstrate the feasibility of microneurography in evaluating SNA in anesthetized small animals, and that the "spontaneous, intermittent burst" signal may be sufficient to identify SNA.

Anesthesia↗