Simvastatin and atorvastatin enhance hypotensive effect of diltiazem in rats

Effects of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in hibitors, simvastatin and atorvastatin, on diltiazem-induced hypotension we re examined in anaesthetized rats and compared to that of pravastatin. Vehi cle, 2 mg/kg/day simvastatin, 2 mg/kg/day atorvastatin, or 4 mg/kg/day prav astatin was administered orally for 4 days. Diltiazem at 3 mg/kg was given orally 2 hours after the final administration of the inhibitors. Arterial b lood pressure was measured via a cannula introduced into the left carotid a rtery, and heart rate was counted from the pulse pressure. In all groups, d iltiazem significantly decreased the mean arterial blood pressure without a ny changes in heart rate. Pretreatment with simvastatin and atorvastatin si gnificantly enhanced the hypotensive effect of diltiazem, while that with p ravastatin did not. Heart rate was not modified by pretreatment with the in hibitors. The results indicate that concomitant use of diltiazem with simva statin or atorvastatin enhances diltiazem-induced hypotension, probably by competitive inhibition of diltiazem metabolism with simvastatin and atorvas tatin metabolisms.