Document Detail

Nitric oxide reduces myocardial contractility in isoproterenol-stimulated rat hearts by a mechanism independent of cyclic GMP or cyclic AMP.
MedLine Citation:
PMID:  9396080     Owner:  NLM     Status:  MEDLINE    
Nitric oxide has been shown to decrease myocardial contractility and O2 consumption. This study was designed to evaluate the hypothesis that nitric oxide-mediated increases in cyclic GMP require elevated cyclic AMP to produce cardiac depression. Using isolated, Langendorff-perfused rat hearts, we determined the effects of intracoronary nitroprusside (NP, 1 and 10 mM) in the absence and presence of isoproterenol (ISO, 10(-8) M) on cardiac function, O2 consumption, cyclic GMP and cyclic AMP. ISO, with and without NP, increased cyclic AMP (from 287 +/- 21 to 477 +/- 33 pmol/g) without altering cyclic GMP. Left-ventricular pressure increased from 97 +/- 12 to 178 +/- 9 mm Hg and dP/dtmax from 1,786 +/- 275 to 4,049 +/- 354 mm Hg/s. NP increased cyclic GMP (from 4 to 30 pmol/g) in both the absence and presence of ISO, but NP did not alter cyclic AMP. Without ISO, NP insignificantly altered left-ventricular pressure; however, in the presence of ISO, NP significantly decreased left-ventricular pressure by -25 +/- 4 mm Hg and decreased dP/dtmax by -619 +/- 142 mm Hg/s. Isoproterenol increased O2 consumption, but the changes with NP were not significant. When this study was repeated in the presence of LY83583, a guanylate cyclase inhibitor, NP still produced cardiac depression in the presence of ISO. Therefore, cardiodepressant effects of NP were only observed against a background of inotropic stimulation with ISO. However, effects of NP on contractility were unrelated to increases in cyclic GMP or cyclic GMP-induced changes in cyclic AMP.
H R Weiss; J D Sadoff; P M Scholz; R E Klabunde
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pharmacology     Volume:  55     ISSN:  0031-7012     ISO Abbreviation:  Pharmacology     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-12-29     Completed Date:  1997-12-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  202-10     Citation Subset:  IM    
Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
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MeSH Terms
Aminoquinolines / pharmacology
Cyclic AMP / physiology*
Cyclic GMP / physiology*
Isoproterenol / pharmacology
Myocardial Contraction / drug effects*
Nitric Oxide / physiology*
Nitroprusside / pharmacology
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
0/Aminoquinolines; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP; 7683-59-2/Isoproterenol; 91300-60-6/6-anilino-5,8-quinolinedione

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

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