STUDIES ON THE EFFECT OF CHRONIC ORAL-ADMINISTRATION OF MINOXIDIL AND HYDRALAZINE ON VASCULAR FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 215  (2) , 279-286
Abstract
Minoxidil [6-imino-1,2-dihydro-1-hydroxy-1-imino-4-piperidino-pyrimidine; U-10858] and hydralazine are related in chemical structure. Minoxidil is effective for the treatment of hypertensive emergencies. The drug lowers total peripheral resistance and has a direct vasodilator action, in vivo, its mechanisms 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 2nd day. The contractile responses of mesenteric arteries and portal veins were measured in vitro. Minoxidil (0.3-10 mg/kg per 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, CaCl2, KCl 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 per day) decreased arterial pressure and depressed the maximal contractile tension and passive stiffness of both mesenteric arteries and portal veins. The antihypertensive action of minoxidil and hydralazine may not be related to a direct depressant action of the drugs on vascular smooth muscle function. Hydralazine and minoxidil, although somewhat similar in structure, may lower blood pressure by 2 different mechanisms. The action of these 2 drugs may be similar but reside in sites other than the vascular smooth muscles studied.