The action of choline on the superior cervical ganglion of the cat.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Ganglionic Blockers”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Drug effects in a novel biphasic writing syndrome induced by acetylcholine in mice.
The writing induced in mice by i.p. administration of 3 mg/kg acetylcholine chloride showed a biphasic response with time. The primary phase of 1-15 sec after acetylcholine appeared to be the result of nicotinic receptor stimulation. The secondary phase from 30 sec following acetylcholine was selectively suppressed by anti-inflammatory agents and by atropine, while centrally acting analgesicw, other strong central nervous system drugs and ganglion blockers suppressed both phases of writhing to an equal extent. The narcotic partial agonists significantly suppressed primary writhing more readily. The method appears to be of value in testing new pharmacological agents.
Acetylcholine↗
Effects of the 5-HT1C/5-5-HT2 receptor agonists DOI and alpha-methyl-5-HT on plasma glucose and insulin levels in the rat.
Administration of the 5-HT1C/5-HT2 receptor agonist 1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane (DOI, 0.125-2.0 mg/kg i.v.) triggered dose-dependent increases in plasma glucose; plasma insulin levels remained unchanged. Pretreatment with the 5-HT1C/5-HT2 receptor antagonists LY 53857, ritanserin, or the mixed 5-HT2/alpha 1-adrenoceptor antagonist ketanserin either diminished or prevented the hyperglycemic effect of DOI (0.5 mg/kg). Administration of the mixed 5-HT1C receptor agonists/5-HT2 receptor antagonists 1-(3-chlorophenyl)-piperazine (mCPP) or 1-(3-trifluoromethyl)phenyl)piperazine level (TFMPP) did not affect plasma glucose levels. However, pretreatment with mCPP or TFMPP decreased DOI-induced hyperglycemia in a dose-dependent manner. The alpha 2-adrenoceptor antagonist idazoxan and the ganglionic blocker hexamethonium both decreased DOI-induced hyperglycemia, Whilst the alpha 1-adrenoceptor antagonist prazosin amplified the rise in plasma glucose elicited by DOI. The peripherally acting 5-HT1C/5-HT2 receptor agonist alpha-methyl-5-HT (0.5-1.0 mg/kg i.v.) triggered a rise in plasma glucose levels that was associated with an increase in plasma insulin levels. Pretreatment with LY 53857 diminished alpha-methyl-5-HT-induced hyperglycemia. These data indicate that 5-HT2 receptors, but not 5-HT1C receptors, and catecholaminergic systems, mediate DOI-induced hyperglycemia. Moreover, it is suggested that the inhibition of insulin release by DOI is centrally mediated, and that activation of peripheral 5-HT2 receptors may affect glycemia.
Amphetamines↗
Direct and indirect effects of angiotensin II on venous tone in conscious rats.
The direct and indirect effects of angiotensin II (ANGII) on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of body venous tone, were investigated in conscious rats. Dose-response curves of ANGII were constructed in control rats (Group I), rats pretreated with saralasin (competitive ANGII antagonist, Group II), with guanethidine (inhibitor of sympathetic postganglionic neurons. Group III), or the ganglionic blocker hexamethonium (Group IV) and rats given unilateral right adrenalectomy two days prior to the study (Group V). The infusion of single doses of ANGII in control, adrenalectomized, guanethidine-treated and hexamethonium-treated rats dose dependently increased MAP to similar maxima; ED50 value was increased by adrenalectomy but unaffected by guanethidine nor hexamethonium. The pressor effects of ANGII was almost completely abolished by saralasin. ANGII dose dependently increased MCFP in control rats. In hexamethonium-treated rats, ANGII also dose relatedly increased MCFP which reached similar maximum as that in control rats, but the ED50 value was reduced. Saralasin almost completely abolished the MCFP response. Both guanethidine and adrenalectomy reduced maximum MCFP response to ANGII, but neither altered the ED50 value. Our results show that the sympathetic nervous system contributed greater to the MCFP than MAP effects of ANGII. Both direct and indirect effects of ANGII are mediated via the activation of ANGII receptors that are susceptible to blockade by saralasin.
Angiotensin II↗
Pentylenetetrazole-induced parasympathetic blood flow increase in the lower lip of the cat.
The pentylenetetrazole (30 mg/kg i.v.)-induced blood flow increase in cat lip was more marked on the sympathectomized side than on the intact side (P < 0.01). This difference is probably dependent on the degree of simultaneous activation of the sympathetic nerve elicited by pentylenetetrazole administration. The blood flow increases were markedly suppressed by prior treatment with hexamethonium (10 mg/kg i.v.), an autonomic ganglion blocker (P < 0.01). Combined section of the facial and glossopharyngeal nerve roots completely abolished the blood flow increases elicited by pentylenetetrazole administration (P < 0.01), but section of either the facial or glossopharyngeal nerve root alone failed to produce complete abolition (P < 0.05). These results indicate that the relevant parasympathetic vasodilator fibers originate not only from the glossopharyngeal, but also the facial nerves and that both participate in pentylenetetrazole-induced vasodilatation in the cat lower lip.
Animals↗
Effects of the 5-HT2C/2B receptor agonist 1-(3-chlorophenyl) piperazine on plasma glucose levels of rats.
Acute administration of the 5-HT2C/2B receptor agonist 1-(3-chlorophenyl)piperazine (mCPP, 5-10 mg/kg i.p.) induced hyperglycemia in rats. These changes were diminished in a dose-dependent manner by the 5-HT1/5-HT2 receptor antagonist methysergide and the 5-HT2A/2B/2C receptor antagonist ritanserin. In addition, mCPP-induced hyperglycemia was dose dependently diminished by the ganglionic blocker hexamethonium and was prevented by prior adrenodemedullation. Neither the 5-HT2A receptor antagonist ketanserin nor the 5-HT3/5-HT4 receptor antagonist (3-alpha-tropanyl)-1 H-indole-3-carboxylic acid ester (ICS 205-930) proved effective against mCPP-induced hyperglycemia. Lastly, administration of the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) increased plasma glucose levels through ketanserin- and ritanserin-sensitive processes. Our results suggest that hyperglycemia elicited by mCPP is mediated by 5-HT2C and/or 2B receptors, and in turn adrenomedullary catecholamine release, whereas that elicited by DOI involves 5-HT2A receptors.
Amphetamines↗
Pharmacologic consequences of the vascular permeability of chromaffin cell transplants in CNS pain modulatory regions.
The transplantation of peripheral neural tissue into the CNS has been shown to alter blood-brain barrier (BBB) permeability to intravascularly injected proteins such as horseradish peroxidase. The pharmacological consequences of such BBB alterations following the transplantation of adrenal medullary tissue, isolated bovine chromaffin cell suspensions, or PC12 cell suspensions into the pain modulatory regions of the periaqueductal gray (PAG) or subarachnoid space of the lumbar spinal cord were studied using agents that normally do or do not readily pass the BBB. The injection of nicotine in animals with adrenal medullary or chromaffin cell transplants produces potent analgesia, most likely due to the stimulated release of opioid peptides and catecholamines from the transplanted cells. This analgesia could be blocked by nicotinic antagonist mecamylamine, which normally passes the BBB, but not by nicotinic antagonist hexamethonium, which normally does not readily pass the BBB. Furthermore, quaternary nicotinic agonists tetramethylammonium and 1,1-dimethyl-phenyl-piperazinium had no effect on pain sensitivity in animals with adrenal medullary implants. The Met-enkephalin peptide analog, D-Ala-Met-enkephalinamide, which normally does not alter pain sensitivity when injected systemically due to limited penetration to the CNS, produced analgesia in animals with adrenal medullary, bovine chromaffin cell, and PC12 cell implants in the PAG, but not in control gelfoam-implanted animals. This analgesia, as well as analgesia induced by nicotine, was completely blocked by naloxone pretreatment, but not by naloxone methobromide, a quaternary derivative of naloxone that does not normally pass the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Medulla↗
Vagal stimulation of rat exocrine pancreatic secretion occurs via multiple mediators.
BACKGROUND: The vagus nerve contains cholinergic and noncholinergic neurons that interact with peptidergic neurons of the enteric nervous system, which stain immunohistochemically for cholecystokinin, vasoactive intestinal polypeptide, and gastrin-releasing peptide. METHODS: The role of these pancreatic exocrine secretagogues during electrical vagal stimulation was studied using specific inhibitors in urethane-anesthetized rats. RESULTS: The pancreatic secretory response to vagal stimulation was blocked significantly by each of the following: the ganglionic blocker hexamethonium (100% inhibition); the muscarinic, cholinergic blocker atropine (85% inhibition); the specific cholecystokinin A-receptor antagonist L-364,718 (84% inhibition); a gastrin-releasing peptide-receptor blocker (91% inhibition); and a vasoactive intestinal polypeptide polyclonal antibody (89% inhibition). The response was not altered by a monoclonal antibody to somatostatin. A subthreshold dose of cholecystokinin octapeptide augmented the response to electrical vagal stimulation. CONCLUSIONS: Suppression of tonic somatostatin release is not the final common event. The findings that subthreshold cholecystokinin augments vagal stimulation, together with marked inhibition by each antagonist used, are consistent with the hypothesis that potentiating interactions among several agonists mediate the vagal response in anesthetized rats. However, this study does not exclude acetylcholine as the final common mediator. Studies in conscious animals are needed to determine the physiological significance of these observations.
Animals↗
Central cardiovascular effects of baclofen in spontaneously hypertensive rats.
This study was conducted to investigate the effects of centrally administered baclofen on blood pressure and heart rate in conscious spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Administration of baclofen (1.0 microgram/kg) into the lateral cerebral ventricle (icv) produced an increase in mean arterial pressure (MAP) in both SHR and WKY rats. The increase in MAP was significantly lower in SHR (13 +/- 3 mmHg) when compared with WKY (27 +/- 5 mmHg). The changes in heart rate (HR) were variable, from no change to a very small increase and did not differ significantly between SHR and WKY rats. The ability of baclofen to interfere with baroreceptor reflexes was also tested in separate experiments. In SHR, icv injection of baclofen (1.0 microgram/kg) significantly suppressed the pressor response and bradycardia evoked by phenylephrine 3.0 micrograms/kg iv, whereas in WKY, the pressor and HR responses to similar injections of phenylephrine were not affected by icv baclofen. Similarly, baclofen treatment modified hypotensive response and reflex tachycardia induced by nitroprusside (10.0 micrograms/kg) iv in SHR but not in WKY rats. Administration of sympathetic ganglionic blocker hexamethonium (HEX; 25 mg/kg) iv produced an equivalent decrease in MAP between SHR and WKY following icv injection of baclofen (1.0 microgram/kg). These results suggest that the effects of baclofen on the baroreceptor reflexes in SHR may not be mediated by a change in peripheral sympathetic tone.
Animals↗
Further studies on the ganglionic and smooth muscle stimulating effect of potassium on the peristaltic reflex of the guinea-pig isolated ileum.
Explore the source record for details and available documents.
Animals↗
Hypothalamic opioid mu-receptors regulate discrete hemodynamic functions in the conscious rat.
The effect of the selective mu-opioid agonist D-Ala2-Me-Phe4-Gly-ol5-enkephalin (DAGO), injected into the medial preoptic nucleus of hypothalamus, on cardiac output and regional blood flow was studied in the conscious rat and the effect of DAGO on renal sympathetic nerve activity and renal blood flow was studied in anesthetized rats. In conscious rats, injections of DAGO (1 or 10 nmol) into the preoptic nucleus increased the blood pressure in a dose-related manner. The maximum rises of mean arterial pressure and pulse pressure after the larger dose were +23 +/- 5 mmHg (mean +/- SEM, P less than 0.01) and +17 +/- 3 mmHg (P less than 0.01), respectively. A small dose (0.1 nmol) increased heart rate (+47 +/- 13 bpm, P less than 0.05); the 1 nmol dose produced bradycardia (-39 +/- 11 bpm, P less than 0.05), while the 10 nmol dose initially decreased heart rate (-68 +/- 15 bpm (P less than 0.01) and then gradually increased heart rate to a maximum of +74 +/- 13 bpm, (P less than 0.01). A long-lasting increase in cardiac output was also elicited by DAGO, with maximum changes after 1 and 10 nmol of +14 +/- 6% and +22 +/- 7% (P less than 0.01), respectively. Blood flow in the hindquarters increased after DAGO but the mesenteric and renal blood flow decreased in a dose-related manner. Significant responses in hindquarter and mesenteric blood flow after DAGO were independent of systemic hemodynamic responses at the dose of 0.1 nmol. The vascular resistance in the hindquarters significantly decreased after a small dose of DAGO while the larger doses dose-dependently increased mesenteric and renal vascular resistance. A crucial role of the sympathetic nervous system in the hemodynamic effects of DAGO was demonstrated: (1) by the profound activation of renal sympathetic nerve activity after injections of DAGO (1 nmol/100 nl) into the preoptic nucleus, (2) by blockade of the pressor, tachycardic and regional hemodynamic effects of DAGO (1 nmol) by the ganglion blocker chlorisondamine (5 mg/kg i.v.). The results suggest that the pressor effect of DAGO in preoptic nucleus is due primarily to an increase in cardiac output. The differential changes in blood flow in organs further suggest that the opioid mu-receptors in the preoptic nucleus might be involved in the integration of peripheral blood flow in the hypothalamus during affective behavior.
Anesthesia↗
Central glucagon-induced hyperglycemia is mediated by combined activation of the adrenal medulla and sympathetic nerve endings.
Intracerebroventricular (ICV) microinjection of glucagon (0.0025-2.5 micrograms) produced significant dose-dependent hyperglycemia in mice. This hyperglycemic effect was prevented by pretreatment with the sympathetic ganglionic blocker chlorisondamine chloride or bilateral adrenalectomy plus chemical sympathectomy with 6-hydroxydopamine. Similar pretreatments had no effect on the plasma glucose responses to systemic glucagon administration. Pretreatment with somatostatin, which blocks pancreatic glucagon secretion had no effect on the hyperglycemic response to central glucagon administration. The results suggest that the increase in plasma glucose following central glucagon administration is mediated by combined action of adrenal and sympathetic amines to stimulate hepatic glucose production, or additionally to inhibit insulin release from the pancreas. The possible involvement of glucagon in the central nervous system in systemic glucoregulation is discussed.
Adrenal Medulla↗
Pharmacological blockade of blood pressure and heart rate increases following milk ingestion in 15-day-old SHR and WKY rat pups.
The effects of hexamethonium, a ganglionic blocker, on blood pressure (BP) and heart rate (HR) responses to milk ingestion were assessed in awake, 15-day-old spontaneously hypertensive rats (SHR) and their normotensive progenitor strain, Wistar-Kyoto rats (WKY) using two methods of milk delivery. SHRs had larger increases in BP compared to WKYs, but WKYs exhibited larger increases in HR following milk ingestion from an anesthetized dam. BP responses to milk ingestion from a tongue cannula were also larger in SHRs. Administration of hexamethonium prior to milk delivery resulted in a drop in BP following milk ingestion in both milk delivery situations for each strain. The results suggest that SHRs exhibit exaggerated sympathetic activation to milk ingestion compared to WKYs, and that in both strains, cardiovascular responses to feeding are modulated by the presence of the dam.
Animals↗
Central and peripheral effects of repeated stress and high NaCl diet on neuropeptide Y.
This study was performed to investigate the influence of repeated psychological stress alone or combined with high NaCl intake on the function of the sympathetic nervous system. In addition, NPY levels have been measured in brain regions of potential importance in the central regulation of stress responses (ventrolateral and dorsomedial medulla, paraventricular and arcuate nucleus of the hypothalamus, and frontal cortex). Normotensive Wistar rats received a standard diet alone or supplemented with NaCl. To accentuate differences in sodium balance, rats on the high NaCl diet (HNa) were uninephrectomized. Half the animals on each diet were subjected to chronic stress using daily sessions (1 h) of immobilization stress. After 12 days, plasma levels of neuropeptide Y (NPY), norepinephrine (NE), and epinephrine (E) were measured basally and in response to acute footshock stress. HNa intake or chronic stress alone did not significantly alter either basal or stimulated plasma levels of NPY. However, combining the treatments produced a significant interaction, increasing the NPY response to footshock by 31% compared to HNa alone (p = 0.039) and by 98% compared to stress alone (p less than 0.001). Chronic stress increased basal levels of NE and enhanced the response to subsequent acute stress: combining the treatments did not yield further increases. Plasma levels of E were not significantly affected by the treatments. In the brain, stress alone had no effect on the NPY levels in the structures studied. HNa intake induced a significant increase in NPY levels of the arcuate nucleus, and produced a significant interaction with stress in the dorsomedial medulla. In a supplementary experiment, to evaluate the role of the autonomic nervous system in plasma NPY responses, treatment with the ganglion blocker hexamethonium was shown to significantly attenuate stress-induced changes in NPY, NE, and E.
Animals↗
Diaphragmatic vasodilation elicited by pulmonary C-fiber stimulation.
This study was performed to assess the effect of pulmonary C-fiber stimulation with capsaicin on vascular resistance in the diaphragm. Nine dogs were anesthetized with pentobarbital sodium and were instrumented with right and left ventricular catheters. The left phrenic artery was isolated and perfused from an extracorporeal reservoir. Right ventricular capsaicin injections (5-20 micrograms/kg) caused significant decreases in phrenic perfusion pressure (-16%), systemic arterial pressure (-32%), and heart rate (-19%). Injection of identical doses of capsaicin into the left ventricle led to no significant changes in phrenic arterial perfusion pressure or systemic arterial pressure but a 10% decrease in heart rate. Bilateral cervical vagotomy eliminated the response to both right and left ventricular injection of capsaicin, as did administration of the autonomic ganglion blocker hexamethonium bromide. The results indicate that pulmonary C-fiber stimulation reflexly vasodilates vessels in the diaphragm.
Animals↗
Cardiovascular effects of anatoxin-A in the conscious rat.
The effects of anatoxin-A on mean arterial pressure (MAP), heart rate, cardiac index (CI), and blood flow (BF) in hindquarter (HQ), renal (R), and mesenteric (M) vascular beds were studied after intravenous (iv) and intracerebroventricular (icv) administration in the conscious rat. The pharmacological profile of anatoxin-A was further compared to nicotine administered iv and icv. MAP and heart rate were measured from femoral artery, CI by thermodilution method, and blood flow by Doppler velocimetry. Anatoxin-A and nicotine (30, 100 and 300 micrograms/kg iv) produced an increase in MAP with concomitant bradycardia. The highest doses increased CI. MBF and RBF decreased due to a vasoconstriction in M and R vasculature. These effects were attenuated by the ganglion blocker chlorisondamine (5 mg/kg, iv). Anatoxin-A (100 micrograms/kg, iv) increased plasma epinephrine levels by 2-fold with virtually no effect on norepinephrine whereas nicotine (100 micrograms/kg, iv) increased plasma epinephrine and norepinephrine by 20- to 30-fold. Central administration of anatoxin-A and nicotine (30-100 micrograms/kg icv) increased MAP with no effect on heart rate and produced M and R vasoconstriction. In summary, the present study demonstrates that anatoxin-A acts as a nicotinic cholinergic agonist in the conscious rat after both systemic and central administration. Anatoxin-A and nicotine produced pressor and reno-splanchnic vasoconstrictor responses and at high doses increased cardiac output. These effects were mediated by activation of the nicotinic receptors in the adrenal medulla and sympathetic ganglia. However, marked differences were found in the potency of anatoxin-A versus nicotine to stimulate the sympathoadrenomedullary axis.
Animals↗
Studies of thyrotropin-releasing hormone (TRH)-induced defecation in cats.
In unanesthetized cats, defecation produced by thyrotropin-releasing hormone (TRH) was investigated after its injection into the cerebral ventricle (ICV) through chronically implanted cannulae. TRH injected in doses from 0.1 to 1.0 mg into the cerebral ventricle evoked defecation which was not dose-dependent. The antimuscarinic drug, atropine, the ganglionic blocker, mecamylamine, the alpha and beta adrenergic blocking agents, yohimbine and propranolol, the dopamine antagonist, chlorpromazine, the 5-hydroxytryptamine antagonist, methysergide, and the antihistamine, antazoline, all injected into the cerebral ventricle had virtually no effect on the defecation evoked by TRH injected similarly. In cats pretreated with ICV reserpine, 5,6-dihydroxytryptamine and hemicholinium-3, the defecation induced by ICV TRH was not significantly changed. On the other hand, in cats pretreated with ICV 6-hydroxydopamine, the defecation caused by ICV TRH was potentiated. Therefore, it is concluded that TRH-induced defecation could not be related to central catecholaminergic, 5-hydroxytryptaminergic and cholinergic receptors, but rather to central TRH sites in the cat.
Animals↗
Influence of various drugs on the variations of blood pressure, hematocrit and plasma histamine caused by neurotensin and compound 48/80 in rats.
Intravenous injections of neurotensin (NT) (0.5, 1 and 2 nmoles kg-1) evoked dose-dependent increases in histaminemia and hematocrit, and marked hypotensive effect, in anesthetized rats. The increase of plasma histamine was rapid in onset (within sec), peak plasma histamine being reached in less than 2 min. The decline of plasma histamine was gradual and almost complete 15 min after injection of NT. The hematocrit increased slowly, maximum values being obtained 5-10 min after injection of NT, and it persisted throughout the period of observation. The hypotensive effect of NT was rapid in onset and of prolonged duration. Compound 48/80, a well known histamine liberator and mast cell depletor, produced variations of blood pressure, of hematocrit and of plasma histamine very similar to those elicited by NT. Pretreatment of rats with cromoglycate, a well known mast cell stabilizer, or with dexamethasone, inhibited markedly the changes of histaminemia, of hematocrit and of blood pressure evoked by NT and compound 48/80. The results clearly suggest that the effects of NT on blood pressure and on vascular permeability in rats are mediated to some extent by mast cell histamine. Hexamethonium, a ganglion blocker, inhibited slightly the effect of NT on histaminemia but it did not block NT-induced changes of hematocrit. However, the hypotensive effect of NT was severely blocked in hexamethonium-treated rats. These results were interpretated as an indication that hexamethonium prevents NT-induced hypotension not merely by reducing the mobilization of mast cell histamine by NT but most likely by interfering with the mechanism by which NT and/or its mast cell mediators produce their effects on blood pressure.
Animals↗