| Nitric oxide and cardiac muscarinic control in humans. | |
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MedLine Citation:
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PMID: 15037554 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiac parasympathetic activity reduces susceptibility to potentially lethal ventricular arrhythmias in heart failure and ischemic heart disease. This influence is mediated in large part by antagonism of the adverse cardiac effects of sympathetic overactivity ("indirect" parasympathetic activity) in addition to the "direct" effects of muscarinic stimulation. Nitric oxide modulates parasympathetic cardiac signaling in some animal models, but human data are lacking. We have investigated the influence of endogenous nitric oxide on cardiac responses to parasympathetic stimulation in healthy humans. In 18 volunteers, we studied chronotropic and inotropic responses to muscarinic stimulation, both before and after prestimulation with isoproterenol. Cardiac muscarinic stimulation was achieved using an intravenous bolus of the short-acting cholinesterase inhibitor, edrophonium. Responses were assessed during a background infusion of a nitric oxide synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA]), placebo (saline), or phenylephrine (vasoconstrictor control) in a single-blind, random order, crossover protocol. L-NMMA did not affect chronotropic responses to edrophonium alone (direct parasympathetic activity). The decrease in heart rate attributable to "indirect" parasympathetic activity (derived by comparison with the effect of edrophonium during concurrent adrenergic stimulation) was substantially attenuated by L-NMMA in comparison to both control infusions. No modification of muscarinic inotropic responses by L-NMMA was apparent in comparison to the vasoconstrictor control. Nitric oxide exerts a powerful facilitating influence on indirect (antiadrenergic) but not direct human cardiac parasympathetic control. Stimulation of the endogenous nitric oxide pathway might enhance parasympathetic protection against the adverse influences of cardiac sympathetic overactivity. |
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Authors:
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Saqib Chowdhary; Anna M Marsh; John H Coote; Jonathan N Townend |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2004-03-22 |
Journal Detail:
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Title: Hypertension Volume: 43 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-05-06 Completed Date: 2004-10-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 1023-8 Citation Subset: IM |
Affiliation:
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Department of Cardiovascular Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH, UK. S.Chowdhary@bham.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adrenergic beta-Agonists / pharmacology Adult Bradycardia / chemically induced Cardiotonic Agents / pharmacology Cholinesterase Inhibitors / pharmacology Cross-Over Studies Edrophonium / pharmacology Enzyme Inhibitors / pharmacology Heart Conduction System / drug effects, physiology* Heart Rate / drug effects Humans Isoproterenol / pharmacology Male Muscarinic Agonists / pharmacology Nitric Oxide / antagonists & inhibitors, physiology* Parasympathetic Nervous System / physiology* Phenylephrine / pharmacology Receptors, Adrenergic, beta-1 / agonists Receptors, Muscarinic / drug effects, physiology* Single-Blind Method Species Specificity Sympathetic Nervous System / physiology Vasoconstrictor Agents / pharmacology omega-N-Methylarginine / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/Cardiotonic Agents; 0/Cholinesterase Inhibitors; 0/Enzyme Inhibitors; 0/Muscarinic Agonists; 0/Receptors, Adrenergic, beta-1; 0/Receptors, Muscarinic; 0/Vasoconstrictor Agents; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 312-48-1/Edrophonium; 59-42-7/Phenylephrine; 7683-59-2/Isoproterenol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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