Abstract
1. Calcium antagonists, including verapamil, are now used widely in the management of patients with hypertension. 2. Six weeks of chronic therapy with verapamil (50 mg/kg per day, orally) to produce a plasma level of 80-100 ng/ml in Sprague-Dawley rats depletes cardiac noradrenaline (NA) without apparently causing beta 1 adrenoceptor 'up' regulation. 3. The effect of verapamil on cardiac NA is rapidly reversed upon verapamil withdrawal. 4. Chronic therapy with nisoldipine (100 mg/kg per day, orally) had no effect on cardiac NA. 5. Verapamil (50 mg/kg per day, orally) and nisoldipine (100 mg/kg per day, orally) therapy for 6 weeks prevented the time-dependent increase in systolic blood pressure in SHR rats. 6. Binding studies with (-)[3H]-D888 (desmethoxyverapamil) indicated that the affinity of the phenylalkylamine binding sites is higher in hearts of SHR relative to hearts from age-matched (25 weeks) WKY and SD, without any change in density.
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