Document Detail

Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy.
MedLine Citation:
PMID:  11748066     Owner:  NLM     Status:  MEDLINE    
Because nitric oxide (NO) regulates cardiac and vessel contraction, we compared the expression and activity of the endothelial NO synthase (eNOS) and caveolin, which tonically inhibits eNOS in normal and hypertrophic cardiomyopathic hearts. NOS activity (L-[(3)H]citrulline formation), eNOS immunostaining, and caveolin abundance were measured in heart tissue of 23 mongrel dogs before and at 3 and 7 wk of perinephritic hypertension (PHT). Hemodynamic parameters in vivo and endothelial NO-dependent relaxation of macro- and coronary microvessels in vitro were assessed in the same animals. eNOS immunostaining and total calcium-dependent NOS activity decreased at 7 wk in all four heart cavities (in left ventricle, from 17.0 +/- 1.3 to 0.2 +/- 0.2 fmol. min(-1). mg protein(-1), P < 0.001). Caveolin-1 and -3 also decreased in PHT dog hearts. Accordingly, basal vascular tone was preserved, but maximal endothelial NO-dependent relaxation was impaired in all vessels from 7-wk PHT dogs. The latter had preserved systolic function but impaired diastolic relaxation [relaxation time constant (T(1)), 25.1 +/- 0.9 vs. 22.0 +/- 1 ms in controls; P < 0.05]. Peripheral infusion of the NOS inhibitor N(G)-nitro-L-arginine methyl ester increased mean aortic pressure in both groups and reduced diastolic (T(1), 31.9 +/- 1.4 ms) and systolic function in PHT dogs (DP40, 47.5 +/- 2.5 vs. 59.4 +/- 3.8 s(-1) in control animals). In conclusion, both eNOS and caveolin proteins are decreased in the hypertrophic hearts of PHT dogs. This is associated with altered maximal (but not basal) vascular relaxation and impaired diastolic function. Further degradation of cardiac function after NOS inhibition suggests a critical role of residual NOS activity, probably supported by the concurrent downregulation of caveolin.
A Piech; P E Massart; C Dessy; O Feron; X Havaux; N Morel; J-L Vanoverschelde; J Donckier; J-L Balligand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  282     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2001-12-18     Completed Date:  2002-01-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H219-31     Citation Subset:  IM    
Unit of Pharmacology and Therapeutics, Dept. of Medicine, FATH 5349, Université Catholique de Louvain, 53, Ave. E. Mounier, B-1200 Brussels, Belgium.
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MeSH Terms
Cardiomyopathy, Hypertrophic / pathology,  physiopathology*
Caveolin 1
Caveolins / metabolism*
Coronary Circulation / physiology
Disease Models, Animal
Hypertension, Renal / physiopathology
Mesenteric Arteries / physiopathology
Microcirculation / drug effects,  physiology
Muscle Contraction
Myocardium / enzymology*,  pathology
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type III
Nitroarginine / pharmacology
Regression Analysis
Ventricular Function, Left / physiology
Reg. No./Substance:
0/Caveolin 1; 0/Caveolins; 2149-70-4/Nitroarginine; 50903-99-6/NG-Nitroarginine Methyl Ester; EC Oxide Synthase; EC Oxide Synthase Type III

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