Studies on the effect of chronic oral administration of minoxidil and hydralazine on vascular function in spontaneously hypertensive rats

S Greeberg

Minoxidil and hydralazine are related in chemical structure. Minoxidil is effective for the treatment of hypertensive emergencies. This drug lowers total peripheral resistance and has a direct vasodilator action, in vivo, its mechanism of action is unknown. The present study evaluated the effects of chronic oral administration of minoxidil and hydralazine on the contractile and passive physical properties of protal veins and small (0.4-0.6 mm outside diameter) mesenteric arteries from spontaneously hypertensive Okamoto-Aoki rats. Minoxidil or hydralazine was added to the drinking water of spontaneously hypertensive rats for 14 days. Blood pressure and heart rate were measured every second day. The contractile responses of mesenteric arteries and portal veins were measured in vitro. Minoxidil (0.3-10 mg/kg/day) produced a dose-related reduction in blood pressure. The in vitro sensitivity (ED50) and maximal contractile tension development of mesenteric arteries to norepinephrine, angiotensin, calcium chloride, potassium chloride and prostaglandins D2, E2, F2 alpha, B2 and A2 were not affected by chronic treatment of spontaneously hypertensive rats with minoxidil. In portal veins, minoxidil did not affect the ED50 or maximal tension development to any agonist. Minoxidil decreased the passive stiffness of portal veins. Hydralazine (1-100 mg/kg/day) decreased arterial pressure and depressed the maximal contractile tension and passive stiffness of both mesenteric arteries and portal veins. The data suggest that the antihypertensive action of minoxidil and hydralazine may not be related to a direct depressant action of the drugs on vascular smooth muscle function. It is possible that hydralazine and minoxidil, although somewhat similar in structure, may lower blood pressure by two different mechanisms. Alternatively, the action of these two drugs may be similar but reside in sites other than the vascular smooth muscles studied.

Volume 215, Issue 2, pp. 279-286, 11/01/1980
Copyright © 1980 by American Society for Pharmacology and Experimental Therapeutics