Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Animals
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Aorta / drug effects
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Aorta / physiopathology
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Arginine / pharmacology*
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Arginine / therapeutic use
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Blood Pressure / drug effects
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / enzymology
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Endothelium, Vascular / physiopathology
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
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Hypertriglyceridemia / drug therapy*
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Hypertriglyceridemia / genetics
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Hypertriglyceridemia / physiopathology
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Male
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Mineralocorticoid Receptor Antagonists / pharmacology*
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Mineralocorticoid Receptor Antagonists / therapeutic use
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / metabolism
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Nitric Oxide Synthase Type III
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Norepinephrine / pharmacology
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Rats
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Rats, Wistar
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Simvastatin / pharmacology*
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Simvastatin / therapeutic use
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Spironolactone / pharmacology*
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Spironolactone / therapeutic use
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Time Factors
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Vasoconstriction / drug effects
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Vasoconstrictor Agents / pharmacology
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Vasodilation / drug effects*
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Vasodilator Agents / pharmacology
Substances
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Mineralocorticoid Receptor Antagonists
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Vasoconstrictor Agents
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Vasodilator Agents
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Spironolactone
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Nitric Oxide
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Arginine
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Simvastatin
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Nitric Oxide Synthase Type II
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Nitric Oxide Synthase Type III
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Nos3 protein, rat
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Acetylcholine
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Norepinephrine