Document Detail

Nitric oxide and cardiac muscarinic control in humans.
MedLine Citation:
PMID:  15037554     Owner:  NLM     Status:  MEDLINE    
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.
Saqib Chowdhary; Anna M Marsh; John H Coote; Jonathan N Townend
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2004-03-22
Journal Detail:
Title:  Hypertension     Volume:  43     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-06     Completed Date:  2004-10-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1023-8     Citation Subset:  IM    
Department of Cardiovascular Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.
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MeSH Terms
Adrenergic beta-Agonists / pharmacology
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
Isoproterenol / pharmacology
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
Reg. No./Substance:
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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