Document Detail

Inhibition of nitric oxide synthase augments myocardial contractile responses to beta-adrenergic stimulation.
MedLine Citation:
PMID:  8997327     Owner:  NLM     Status:  MEDLINE    
Recent in vitro evidence suggests a role for nitric oxide (NO) in the modulation of myocardial contractility. The specific role of NO in the control of cardiac function in vivo, however, remains unclear. We investigated the effect of NO synthase (NOS) inhibition on myocardial contractility in response to beta-adrenergic stimulation in autonomically blocked dogs. Intracoronary infusions of dobutamine (1-50 micrograms/min) and isoproterenol (0.1 and 0.5 microgram/min) were performed before and after the intracoronary administration of the specific NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Intracoronary dobutamine resulted in a dose-dependent increase in peak first derivative of pressure (dP/dtmax) to a maximum of 195 +/- 10% (P < 0.001). After inhibition of NOS with intracoronary L-NAME at rates of 0.1 and 1 mg/min, the response to dobutamine was significantly enhanced with dP/dtmax, increasing 276 +/- 17 and 317 +/- 26%, respectively (P < 0.001). Intracoronary isoproterenol resulted in a maximum increase in dP/dtmax of 116 +/- 15% (P < 0.001) that further increased to 154 +/- 17 and 157 +/- 18% after NOS inhibition with 0.1 and 1 mg/min L-NAME, respectively (both P < 0.002). L-NAME had no effect on baseline dP/dtmax but did produce a reduction in myocardial guanosine 3',5'-cyclic monophosphate content. These results suggest a role for NO in the control of myocardial contractility in response to beta-adrenergic stimulation in vivo.
J F Keaney; J M Hare; J L Balligand; J Loscalzo; T W Smith; W S Colucci
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  271     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-02-20     Completed Date:  1997-02-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H2646-52     Citation Subset:  IM    
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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MeSH Terms
Adrenergic beta-Agonists / pharmacology*
Coronary Vessels
Cyclic GMP / metabolism
Dobutamine / pharmacology
Enzyme Inhibitors / pharmacology
Heart / drug effects*
Isoproterenol / pharmacology
Myocardial Contraction*
Myocardium / metabolism
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors*
Ventricular Function
Grant Support
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Enzyme Inhibitors; 34368-04-2/Dobutamine; 50903-99-6/NG-Nitroarginine Methyl Ester; 7665-99-8/Cyclic GMP; 7683-59-2/Isoproterenol; EC Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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