Pravastatin affects blood pressure and vascular reactivity.
To investigate the effect of endogenous cholesterol synthesis on blood pressure and vascular response, a HMG CoA reductase inhibitor, pravastatin (1 or 10 mg/kg per day) was administered orally for 2 or 4 weeks to spontaneously hypertensive rats (SHR/lzm) and normotensive Wistar-Kyoto (WKY/lzm) rats. Blood pressure was significantly increased in the pravastatin-treated groups of both strains, occurring in WKY after a longer treatment period than in SHR. The thoracic aortas from SHR and WKY were pretreated with pravastatin (10(-4)M). The vascular response to norepinephrine in terms of both contractility and sensitivity, was increased in the pravastatin-treated SHR aorta but not in the WKY aorta. The increased response was not observed in the presence of mevalonate. Acetylcholine-induced vascular relaxation in the aortas from both strains was not affected by pravastatin pretreatment. These results suggest that the vascular response to norepinephrine may be affected by the intracellular cholesterol synthesis pathway.
Li
N
N
Graduate School of Human and Environmental Studies, Kyoto University, Japan.
Sawamura
M
M
Nara
Y
Y
Ikeda
K
K
Yamori
Y
Y
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D017035:Pravastatin; D008798:Mevalonic Acid; D009638:Norepinephrine