Hypotensive and diuretic actions of diltiazem in spontaneously hypertensive and Wistar Kyoto rats.

We investigated the hypotensive and diuretic effects of diltiazem and hydralazine in conscious, spontaneously hypertensive rats (SHR) and their counterpart, Wistar Kyoto rats (WKY). Orally administered diltiazem induced dose-dependent hypotension both in SHR (10-60 mg/kg) and in WKY (30-100 mg/kg) and the effects were more pronounced in SHR than in WKY. Diltiazem did not cause tachycardia in either strain. Moreover, hypotensive doses of diltiazem acutely increased urinary excretion of sodium as well as urine volume in saline-loaded SHR and WKY. Chronic administration of diltiazem (30 mg/kg/day for 8 weeks) to young SHR caused no changes in body fluid distribution or in plasma sodium concentration. On the other hand, hydralazine not only showed almost the same hypotensive potency in SHR and WKY but also resulted reflex tachycardia in both strains. In addition, hydralazine (5 mg/kg) decreased urinary sodium excretion in saline-loaded SHR. In conclusion, it was suggested that diltiazem is an antihypertensive agent with an enhanced hypotensive action in the hypertensive state and without tachycardia and sodium retention effects.