|Comparison of the effect of simvastatin, spironolactone and L-arginine on endothelial function of aorta in hereditary hypertriglyceridemic rats.|
|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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|Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2007-09-05|
|Title: Physiological research / Academia Scientiarum Bohemoslovaca Volume: 56 Suppl 2 ISSN: 0862-8408 ISO Abbreviation: Physiol Res Publication Date: 2007|
|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|
|Languages: eng Pagination: S33-40 Citation Subset: IM|
|Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovakia. Jozef.Torok@savba.sk|
|APA/MLA Format Download EndNote Download BibTex|
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
Simvastatin / pharmacology*, therapeutic use
Spironolactone / pharmacology*, therapeutic use
Vasoconstriction / drug effects
Vasoconstrictor Agents / pharmacology
Vasodilation / drug effects*
Vasodilator Agents / pharmacology
|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 184.108.40.206/Nitric Oxide Synthase Type II; EC 220.127.116.11/Nitric Oxide Synthase Type III; EC 18.104.22.168/Nos3 protein, rat|
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