Abstract
The mode of a transient hypotensive action of d!-Mandelamidine (MA) was studied in both anesthetized and unanesthitized animals. In the blood pressure of unanesthetized rats, a transient hypotensive action of MA (1 ?? 30 mg/kg i.v.) like papaverine (1 ?? 10 mg/kg i.v.) was much less predominant than in rats anesthetized with urethane (1.5 g/kg s.c.). The transient hypotensive action of MA (10 mg/kg i.v.) in rats anesthetized with urethane (1.5 g/kg s.c.) was not reduced when MA was injected continuously. Moreover C6 (5 mg/kg i.v.), propranolol (1 mg/kg i.v.), diphenhydramine (10 mg/kg i.v.) and atropine (2 mg/kg i.v.) did not block this transient hypotensive action. MA blocked the pressor action of epinephrine (3 μg/kg i.v.) in three minutes, but then potentiated it. MA (10 μg/kg i.a. ?? 1 mg/kg i.a.) caused a temporary vasodilation on the perfused leg artery and vertebral artery in dogs anesthetized with sodium pentobarbital (30mg/kg i.v.). In the perfused leg artery, atropine (2 mg/kg i.v.) and propranolol (1 mg/kg i.v.) did not block the vasodilation of MA, and MA showed no marked blocking effect of the vasoconstriction of norepinephrine (0.2 μg/kg i.a.). In the dog heart-lung preparation and the guinea-pig heart, MA showed inhibiting effects. On the contraction of the cat nictitating membrane elicited by the stimulation of the postganglionic cervical sympathetic nerve, the blocking action of MA (1μg/kg i.a. ?? 1 mg/kg i.a) was much less predominant than that of phentolamine (10μg/kg i.a.). In the rabbit descending aorta, MA (3×10-4g/ml) antagonized non-competitively the contraction elicited by norepinephrine. These findings suggest that a transient hypotensive action of MA depends upon the inhibiting effects on the cardiovascular system, and the adrenergic α-blocking effect of MA may be very weak.
