Document Detail


Negative metabolic effects of cyclic GMP are altered in renal hypertension induced cardiac hypertrophy.
MedLine Citation:
PMID:  9062647     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O2 consumption and that renal hypertension (One Kidney-One Clip, 1K1C)-induced cardiac hypertrophy would change this relationship. Four groups of anesthetized open-chest New Zealand white rabbits (N = 26) were utilized. Either vehicle or 3-morpholinosydnonimine (SIN-1) (10(-4) M, a guanylate cyclase activator) was topically applied to the left ventricular surface of control or 1K1C rabbits. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine O2 consumption. Myocardial cyclic GMP levels were determined by radioimmunoassay. Guanylate cyclase activity was measured by conversion of GTP to cyclic GMP. 1K1C rabbits had a greater heart weight-to-body weight ratio (3.29 +/- 0.15) than controls (2.63 +/- 0.19). Systolic blood pressure was higher in 1K1C rabbits than in controls. In control rabbits, cyclic GMP levels (pmoles/g) were higher in SIN-1-treated (EPI: 7.5 +/- 1.6; ENDO: 8.1 +/- 1.5) than in vehicle-treated animals (EPI: 5.4 +/- 0.4; ENDO: 5.6 +/- 0.6). This effect was enhanced in 1K1C rabbits, with cyclic GMP levels in the SIN-1-treated group (EPI: 11.9 +/- 1.3; ENDO: 13.0 +/- 1.5) almost double those observed in the vehicle-treated group (EPI: 6.3 +/- 0.8; ENDO: 7.7 +/- 1.1). There were no significant differences in basal or maximally stimulated guanylate cyclase activity between controls and 1K1C rabbits. Myocardial O2 consumption (ml O2/min/100 g) was significantly less in the EPI region of control animals treated with SIN-1 (7.2 +/- 1.2) than in the same region of controls treated with vehicle (9.1 +/- 2.0). Myocardial O2 consumption was also significantly less in SIN-1-than vehicle-treated 1K1C animals (SIN-1-treated: EPI: 6.9 +/- 0.8; ENDO: 6.2 +/- 0.7; vehicle-treated: EPI: 10.0 +/- 0.8; ENDO: 12.5 +/- 3.0). There was no significant difference in O2 consumption between control and 1K1C animals after treatment with SIN-1. Thus, there was a greater elevation in cyclic GMP in 1K1C rabbits, but this did not result in a corresponding greater depression in O2 consumption. This suggests that cyclic GMP plays a role in the control of myocardial metabolism, and that the sensitivity of myocardial O2 consumption to changes in cyclic GMP is reduced by renal hypertension-induced cardiac hypertrophy.
Authors:
P Rabindranauth; K L Naim; P M Scholz; J Tse; J D Sadoff; H R Weiss
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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:  Basic research in cardiology     Volume:  92     ISSN:  0300-8428     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-05-22     Completed Date:  1997-05-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  8-16     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Gas Analysis
Cardiomegaly / metabolism*
Coronary Circulation / drug effects
Cyclic GMP / analysis,  metabolism*
Enzyme Inhibitors / pharmacology
Guanylate Cyclase / metabolism
Hemodynamics / drug effects
Hypertension, Renovascular / metabolism*
Molsidomine / analogs & derivatives,  pharmacology
Myocardium / chemistry,  metabolism*
Oxygen / metabolism
Rabbits
Grant Support
ID/Acronym/Agency:
HL40320/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 25717-80-0/Molsidomine; 33876-97-0/3-morpholino-sydnonimine; 7665-99-8/Cyclic GMP; 7782-44-7/Oxygen; EC 4.6.1.2/Guanylate Cyclase

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