The effect of amlodipine on hypertension-induced cardiac hypertrophy and reperfusion-induced calcium overload.

Abstract

Amlodipine is a long-acting dihydropyridine-based calcium antagonist developed for use on a once-a-day basis. Experiments were undertaken to establish whether the chronic administration of amlodipine prevents the rise in blood pressure in spontaneously hypertensive rats (SHR), and whether it attenuates cardiac hypertrophy caused by hypertension. The experiments were performed in spontaneously hypertensive rats, and normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. Amlodipine was given orally to provide a daily intake of 10 mg kg-1 day-1. The rats were 8 weeks old at the start of the therapy. In the SHR, but not in the WKY or SD rats, the blood pressure was reduced (p less than 0.01) after 30 weeks in the rats receiving amlodipine but not in the placebo-treated rats. At the same time the heart-to-body-weight ratio was reduced in the amlodipine-treated SHR but not in the SD or WKY rats. This same amlodipine regimen (10 mg kg-1 day-1 orally) or amlodipine i.v. (0.25 mg/kg, 5 h before excising the hearts) improved functional recovery (p less than 0.01) of hearts "stunned" by 10 min ischemia and attenuated (p less than 0.05) calcium ion gain on reperfusion after 30 to 60 min ischemia. These results indicate that prophylactic therapy with amlodipine lowers blood pressure in hypertensive rats, prevents hypertension-induced hypertrophy, and exerts a cardiac-protective effect during short periods of ischemia.