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Decreasing cyclic GMP exerts similar positive functional effects on cardiac myocytes regardless of initial level.
MedLine Citation:
PMID:  10895081     Owner:  NLM     Status:  MEDLINE    
We tested the hypothesis that lowering the level of cyclic GMP would have positive functional effects on isolated rabbit ventricular myocytes regardless of the basal cyclic GMP level. Cell shortening data were collected with a video detector; O(2) consumption data were obtained with a Clark electrode; intracellular cyclic GMP levels were obtained by radioimmunoassay. Data were obtained: (1) at baseline; (2) after the addition of 1H-[1,2,4]oxadiazolo[4, 3-alpha]quinoxaline-1-one (ODQ) 10(-6) and 10(-4) mol/l, a selective soluble guanylyl cyclase inhibitor, and (3) after zaprinast 10(-6) mol/l, a cyclic GMP phosphodiesterase inhibitor, followed by ODQ 10(-6) and 10(-4) mol/l. We found that ODQ 10(-4) mol/l significantly decreased the cyclic GMP level from 493 +/- 75 to 301 +/- 78 (fmol/100,000 myocytes) and increased percent shortening (Pcs, %; 4.9 +/- 0.3 vs. 5.8 +/- 0.6) and maximum rate of shortening (Rs, microm/s; 58.7 +/- 5.7 vs. 73.6 +/- 4.9). Zaprinast significantly increased the cyclic GMP level from 419 +/- 140 to 599 +/- 241 and decreased Pcs (6.2 +/- 0.5 vs. 4.4 +/- 0.4) and Rs (65.5 +/- 5.3 vs. 49.6 +/- 4.3). After zaprinast, ODQ 10(-4) mol/l decreased the cyclic GMP level to 439 +/- 139 and increased percent shortening and rate of shortening by a similar percentage compared to the non-zaprinast treated myocytes. We conclude that in rabbit ventricular myocytes, a reduction in the level of myocyte cyclic GMP increases myocyte function independent of the initial cyclic GMP level.
L Yan; M W Huang; P M Scholz; H R Weiss
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pharmacology     Volume:  61     ISSN:  0031-7012     ISO Abbreviation:  Pharmacology     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-24     Completed Date:  2000-08-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  51-6     Citation Subset:  IM    
Copyright Information:
Copyright 2000 S. Karger AG, Basel
Heart and Brain Circulation Laboratory, Departments of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA.
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MeSH Terms
Cyclic GMP / analysis,  physiology*
Guanylate Cyclase / metabolism
Heart / physiology*
Myocardium / cytology,  metabolism
Oxadiazoles / pharmacology
Oxygen Consumption / drug effects
Purinones / pharmacology
Quinoxalines / pharmacology
Grant Support
Reg. No./Substance:
0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Oxadiazoles; 0/Purinones; 0/Quinoxalines; 37762-06-4/zaprinast; 7665-99-8/Cyclic GMP; EC Cyclase

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