Effects of urapidil on blood pressure and adrenoceptors in various animal models

The interaction with alpha- and beta-adrenoceptors, and the antihypertensive and hypotensive effects of urapidil were studied in various animal models. Urapidil reduced the mean arterial pressure (MAP) of conscious normotensive and spontaneously hypertensive rates after oral administration. Urapidil antagonized alpha 1- and alpha 2-adrenoceptor-mediated vasoconstriction in pithed rats, elicited by cirazoline and B-HT 920, respectively. Urapidil itself caused pressor responses of limited magnitude at high doses in pithed rats, which were not blocked by yohimbine, prazosin or ketanserin. Urapidil displayed partial beta 1-adrenoceptor intrinsic activity in pithed rats. Urapidil was more potent in reducing MAP after infusion via the vertebral artery as compared to infusion via the femoral artery of chloralose-anaesthetized cats. The results suggest that urapidil reduces blood pressure via blockade of peripheral vascular alpha-adrenoceptors, and beta-receptor blockade. A centrally mediated hypotension not involving alpha 2-adrenoceptors may contribute to the antihypertensive effect.