Simvastatin and atorvastatin enhance hypotensive effect of diltiazem in rats.
Effects of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, simvastatin and atorvastatin, on diltiazem-induced hypotension were examined in anaesthetized rats and compared to that of pravastatin. Vehicle, 2 mg/kg/day simvastatin, 2 mg/kg/day atorvastatin, or 4 mg/kg/day pravastatin was administered orally for 4 days. Diltiazem at 3 mg/kg was given orally 2 hours after the final administration of the inhibitors. Arterial blood pressure was measured via a cannula introduced into the left carotid artery, and heart rate was counted from the pulse pressure. In all groups, diltiazem significantly decreased the mean arterial blood pressure without any changes in heart rate. Pretreatment with simvastatin and atorvastatin significantly enhanced the hypotensive effect of diltiazem, while that with pravastatin did not. Heart rate was not modified by pretreatment with the inhibitors. The results indicate that concomitant use of diltiazem with simvastatin or atorvastatin enhances diltiazem-induced hypotension, probably by competitive inhibition of diltiazem metabolism with simvastatin and atorvastatin metabolisms.
Marumo
H
H
Department of Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka, Otaru 047-0264, Japan.
Satoh
K
K
Yamamoto
A
A
Kaneta
S
S
Ichihara
K
K
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D004110:Diltiazem; D017035:Pravastatin