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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guanine nucleotide binding proteins couple a wide variety of receptors to ion channels via both "direct" or membrane-delimited and "indirect" second messenger-mediated pathways. This tutorial summarizes current approaches to defining the mechanisms of guanine nucleotide binding protein-mediated ion channel activation. Two well-characterized ion channels in the heart, namely, the beta-adrenergic receptor-activated calcium channel and the muscarinic receptor-activated potassium channel, are used to illustrate the criteria that can distinguish between direct and indirect guanine nucleotide binding protein-transduced pathways.
Hypertension 1991 May
PMID:G protein-mediated ion channel activation. 170 43

In the lateral septal area of spontaneously hypertensive rats, but not in Wistar-Kyoto rats, the selective M1 antagonist, pirenzepine, and the depletion of acetylcholine storage, by hemicholinium-3 (HC-3), decreased blood pressure. The selective M1 agonist McNeil-A-343, produced a pressor response only after treatment of the lateral septal area with HC-3 in spontaneously hypertensive rats. Carbachol, at doses that mainly affect M2 muscarinic receptors, caused no cardiovascular changes in either strain, pointing to the main intervention of the M1 subtype of muscarinic receptor in the hypertensive condition. In addition, increases in the density of binding sites for [3H]QNB and in Vmax of sodium-dependent, HC-3-inhibitable, high affinity uptake of choline were demonstrated, without significant changes of the activity of choline acetyltransferase in the lateral septal area of spontaneously hypertensive rats. These results suggest that a hyperactivity of the cholinergic system of this area could play a role in the development and/or maintenance of hypertension in spontaneously hypertensive rats.
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PMID:Cholinergic hyperactivity in the lateral septal area of spontaneously hypertensive rats: depressor effect of hemicholinium-3 and pirenzepine. 171 27

This study determined the influence of pentobarbital anesthesia on the autonomic nervous system control of baroreceptor mediated reflex bradycardia in the rat. Reflex bradycardia was elicited by phenylephrine-induced hypertension in conscious and pentobarbital anesthetized (PA) rats before and after sympathetic blockade with the beta-1 receptor antagonist atenolol or parasympathetic blockade with the peripherally acting muscarinic receptor antagonist methyl-atropine. Reflex bradycardia was significantly decreased by pentobarbital anesthesia. Cardiosympathetic blockade produced equivalent relative decreases in baroreflex gain in conscious and PA rats. In contrast, parasympathetic nervous system blockade with methyl-atropine produced relatively less inhibition of baroreflex gain in the PA rat compared with the conscious rat. These results suggest that pentobarbital anesthesia decreases baroreflex gain by inhibiting vagally mediated reflex bradycardia.
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PMID:The effect of pentobarbital anesthesia on the autonomic nervous system control of heart rate during baroreceptor activation. 176 16

Key discoveries in the past decade revealed that the endothelium can modulate the tone of underlying vascular smooth muscle by the synthesis/release of potent vasorelaxant (endothelium-derived relaxing factors; EDRF) and vasoconstrictor substances (endothelium-derived contracting factors; EDCF). It has become evident that the synthesis and release of these substances contribute to the multitude of physiological functions the vascular endothelium performs. Accumulating evidence suggests that at least one of the EDRFs is identical with nitric oxide (NO) or a labile nitroso compound, which is produced from L-arginine by an NADPH- and Ca(2+)-dependent enzyme, arginine oxidase. The existence of more than one chemically distinct EDRF has been proposed, including an endothelium-derived hyperpolarizing factor (EDHF). The target of EDRF (NO) is soluble guanylate cyclase (increase in cyclic GMP) while EDHF appears to activate a K(+)-channel in vascular smooth muscle. Recent data suggest that muscarinic receptor subtypes selectively mediate the release of EDRF(NO) (M2) and EDHF (M1). EDRF(NO) affects not only the underlying vascular smooth muscle, but also platelets, inhibiting their aggregation and adhesion to the endothelium. The antiaggregatory effect of EDRF is synergistic with prostacyclin, so their combined release may represent a physiological mechanism aimed at preventing thrombus formation. An additional proposed biological function of EDRF(NO) is cytoprotection by virtue of scavenging superoxide radicals. The endothelium can also mediate vasoconstriction by the release of a variety of endothelium-derived contracting factors (EDCF). Other than the unique peptide endothelin, the nature of EDCFs has not yet been firmly established. Autoregulation of cerebral and renal blood flow and hypoxic pulmonary vasoconstriction may represent the physiological role of endothelium-dependent vasoconstriction. Growing evidence indicates that the endothelium can serve as a unique mechanoreceptor, sensing and transducing physical stimuli (e.g., shear forces, pressure) into changes in vascular tone by the release of EDRFs or EDCFs. In physiological states, a delicate balance exists between endothelium-derived vasodilators and vasoconstrictors. Alterations in this balance can result in local (vasospasm) and generalized (hypertension) increase in vascular tone and also in facilitated thrombus formation. Endothelial dysfunction may also contribute to the pathophysiology of angiopathies associated with hypercholesterolemia and atherosclerosis.
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PMID:Endothelium-derived relaxing and contracting factors. 187 96

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.
Hypertension 1989 Jun
PMID:Role of vasopressin in cardiovascular response to central cholinergic stimulation in rats. 273 6

The ontogeny of functional sympathetic neural, adrenal medullary, and extra-adrenal components of adrenergic control of heart rate was compared in neonatal Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Borderline hypertensive (BHR) rats using combined sequential pharmacological blockade and surgical intervention. Baseline heart rate recorded from awake and unrestrained pups was lower in BHR than in WKY or SHR at 5 days of age. Tonic sympathetic neural control of heart rate was inferred from bradycardia after treatment with the adrenergic neuron-blocking agent, bretylium tosylate. Bradycardia after bretylium treatment was observed at 2, 5 and 8 days of age in all strains, suggesting tonic sympathetic neural control of heart rate during the first postnatal week. Parasympathetic control of heart rate was inferred from heart rate increase after treatment with the muscarinic receptor blocker, atropine methyl nitrate, in pups pretreated with bretylium. Tachycardia following atropine methyl nitrate was substantial in all 24-day-old pups. Control of heart rate by neurally mediated release of catecholamines from the adrenal medulla was inferred from bradycardia following administration of the ganglionic blocking agent, hexamethonium, to pups pretreated with bretylium and atropine methyl nitrate. Heart rate decreases after hexamethonium were found in 2-day-old WKY and BHR pups, and at 5 and 8 days in all strains. Adrenalectomy was performed in additional animals to confirm the adrenal catecholamine influence on heart rate. The influence of residual circulating catecholamines on neonatal heart rate was inferred from bradycardia following administration of the beta-adrenergic receptor blocking agent, atenolol, in pups pretreated with bretylium, methylatropine, and hexamethonium. Bradycardia was observed in pups of each strain and at all ages after atenolol treatment. Strain differences in autonomic controls of heart rate were most pronounced at 24 days of age. At 24 days of age both SHR and BHR pups showed increased adrenal catecholamine and parasympathetic influences on heart rate compared to WKY. Thus, prior to weaning, rats differing in their genetic predisposition to hypertension showed a unique pattern of autonomic control over heart rate which may be related to adult cardiovascular regulation.
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PMID:Balance among autonomic controls of heart rate in neonatal spontaneously hypertensive and borderline hypertensive rats. 289 29

The cardiovascular effects induced in the rat by several muscarinic receptor agonists were studied. All the agonists produced a clear decrease in heart rate. This decrease appeared to be peripherally mediated, because it was antagonized by methylscopolamine. The effects on blood pressure varied depending on the presence of anaesthesia, previous treatments and the type of agonists tested. When peripheral muscarinic activity was blocked by administration of methylscopolamine, a dose-dependent hypertension was obtained following the injection of oxotremorine, arecoline and aceclidine, by both intraperitoneal and intracerebroventricular routes. The muscarinic receptor agonist RS 86 produced a slight increase in blood pressure but the increase was weaker than those observed with the agonists cited above. On the other hand, the muscarinic receptor agonists pilocarpine, AF-30 and McN-A-343, considered as partially M1-selective compounds, did not produce any effect on blood pressure. Moreover, the hypertension induced by oxotremorine was completely blocked by intracerebroventricular administration of the non-subtype-selective muscarinic receptor antagonist scopolamine but was unaffected by the M1-selective antagonist pirenzepine. We propose that the central hypertensive response induced by muscarinic receptor agonists in the unanaesthetized rat is, at least partially, mediated through the stimulation of the so-called M2 muscarinic receptor subtype.
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PMID:Central pressor effects induced by muscarinic receptor agonists: evidence for a predominant role of the M2 receptor subtype. 373 92

The present study describes developmental changes in autonomic controls of heart rate in a strain of rats genetically predisposed to hypertension (spontaneously hypertensive rats or SHR) and in a normotensive strain of rats (Wistar-Kyoto rats or WKY). Rat pups were tested at 4, 8, 12, and 16 days to determine heart rate changes after selective pharmacological treatments. Specifically, freely moving pups were treated with selective beta-adrenergic and muscarinic receptor blockers (i.e., atenolol and atropine methylnitrate), using procedures designed to produce minimal pain or discomfort. The results indicated that by 4 days of age there is a substantial sympathetic acceleratory influence on heart rate. Comparison of inferred autonomic control of the heart in prehypertensive SHR and normotensive WKY pups suggested exaggeration of this early sympathetic influence among SHR pups. After 2 wk of age, however, equivalent autonomic control of heart rate was seen in SHR and WKY rats, with the higher basal heart rate of SHR rats being mediated by an increased intrinsic heart rate (i.e., heart rate after combined blockade). These findings suggest that enhanced sympathetic nervous system activity may be an early expression of the genetic predisposition to develop hypertension.
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PMID:Development of autonomic control of heart rate in genetically hypertensive and normotensive rats. 614 73

Evidence is presented that implicates brain acetylcholine (ACh) in the control of blood pressure (BP) and in hypertension. Central cholinergic stimulation by muscarinic agonists or inhibitors of acetylcholinesterase (AChE) evokes a hypertensive response in several animal species, including humans. The elevation in BP after injection of AChE inhibitors is mediated centrally by ACh acting on muscarinic receptors and peripherally through increased sympathetic nerve activity. The pressor response is accompanied by inhibition of reflex tachycardia and potentiation of both reflex bradycardia and the pressor reflex to carotid artery occlusion. Intracerebroventricular injection of hemicholinium 3 in doses that deplete brain ACh lowers BP in the spontaneously hypertensive and the deoxycorticosterone acetate-salt hypertensive rat. Little or no reduction occurs in the normotensive rat or in animals made hypertensive by aortic coarctation. In addition, atropine and the selective central muscarinic receptor antagonist N-(4-diethylamino-2-butynyl)-succinimide lower BP in the spontaneously hypertensive rat but not in the normotensive rat.
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PMID:Cardiovascular regulation by brain acetylcholine. 669 Mar 34

The density of muscarinic receptor sites, choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activity in the myocardium of the Dahl salt-sensitive (DS) and salt-resistant (DR) rat was investigated. Both normotensive and hypertensive (as a result of 8.0% NaCl added to the diet) DS rats displayed a lower concentration of muscarinic receptors and less ChAT and AChE activity in myocardial tissue than normotensive DR rats. Lower receptor site density and enzyme activity in the myocardial of the DS line may reflect decreased vagal tone. If true, this may produce dificits in the ability to appropriately adjust heart rate (HR) in response to elevations in blood pressure (BP). Therefore, the present results may be viewed as exacerbational factors in the pathogenesis of hypertension in the DS line.
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PMID:Myocardial cholinergic receptor sites and enzyme activity in the Dahl model of essential hypertension. 672 89


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