Document Detail

Comparison of the effect of simvastatin, spironolactone and L-arginine on endothelial function of aorta in hereditary hypertriglyceridemic rats.
MedLine Citation:
PMID:  17824809     Owner:  NLM     Status:  MEDLINE    
Hereditary hypertriglyceridemic (hHTG) rats are characterized by increased blood pressure and impaired endothelium-dependent relaxation of conduit arteries. The aim of this study was to investigate the effect of long-term (4 weeks) treatment of hHTG rats with three drugs which, according to their mechanism of action, may be able to modify the endothelial function: simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase), spironolactone (an antagonist of aldosterone receptors) and L-arginine (a precursor of nitric oxide formation). At the end of fourth week the systolic blood pressure in the control hHTG group was 148+/-2 mm Hg and in control normotensive Wistar group 117+/-3 mm Hg. L-arginine failed to reduce blood pressure, but simvastatin (118+/-1 mm Hg) and spironolactone (124+/-4 mm Hg) treatment significantly decreased the systolic blood pressure. In isolated phenylephrine-precontracted aortic rings from hHTG rats endothelium-dependent relaxation was diminished as compared to control Wistar rats. Of the three drugs used, only simvastatin improved acetylcholine-induced relaxation of the aorta. We conclude that both simvastatin and spironolactone reduced blood pressure but only simvastatin significantly improved endothelial dysfunction of aorta. Prominent increase in the expression of eNOS in large conduit arteries may be the pathophysiological mechanism underlying the protective effect of simvastatin in hHTG rats.
J Török; I L'upták; J Matúsková; O Pechánová; J Zicha; J Kunes; F Simko
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-05
Journal Detail:
Title:  Physiological research / Academia Scientiarum Bohemoslovaca     Volume:  56 Suppl 2     ISSN:  0862-8408     ISO Abbreviation:  Physiol Res     Publication Date:  2007  
Date Detail:
Created Date:  2008-01-16     Completed Date:  2008-04-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9112413     Medline TA:  Physiol Res     Country:  Czech Republic    
Other Details:
Languages:  eng     Pagination:  S33-40     Citation Subset:  IM    
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovakia.
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MeSH Terms
Acetylcholine / pharmacology
Aldosterone Antagonists / pharmacology*,  therapeutic use
Aorta / drug effects,  physiopathology
Arginine / pharmacology*,  therapeutic use
Blood Pressure / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects*,  enzymology,  physiopathology
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*,  therapeutic use
Hypertriglyceridemia / drug therapy*,  genetics,  physiopathology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / metabolism
Nitric Oxide Synthase Type III
Norepinephrine / pharmacology
Rats, Wistar
Simvastatin / pharmacology*,  therapeutic use
Spironolactone / pharmacology*,  therapeutic use
Time Factors
Vasoconstriction / drug effects
Vasoconstrictor Agents / pharmacology
Vasodilation / drug effects*
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Aldosterone Antagonists; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 51-41-2/Norepinephrine; 51-84-3/Acetylcholine; 52-01-7/Spironolactone; 74-79-3/Arginine; 79902-63-9/Simvastatin; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC protein, rat

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

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