THE CARIDIOVASCULAR EFFECTS OF 6,7-DIMETHOXY-4-HYDROXY-QUINOLINE HYDROCHLORIDE (U-558)

¹ Section of Pharmacology, Eaton Laboratories Division, The Norwich Pharmacal Company, Norwich, New York

U-558 (6,7 - dimethoxy - 4 - hydroxyquinoline hydrochloride) significantly reduced the blood pressure of unanesthetized renal hypertensive dogs and normotensive anesthetized dogs, rats, cats, rabbits and monkeys when given by the oral or intravenous routes. In the anesthetized dog, the hypotensive effect of U-558 was usually associated with an increase in heart rate, a delayed reduction in cardiac output and an increase in right ventricular contractile force. The hypotensive effect of U-558 was not abolished by dichloroisoproterenol, atropine, reserpine, guanethidine, Dibenamine or vagotomy plus carotid sinus denervation. During the hypotensive effects of U-558, the reflex rise in blood pressure produced by bilateral carotid artery occlusion was reduced. The pressor effects of epinephrine, norepinephrine and angiotensin II were similarly inhibited by U-558. Also inhibited by U-558 was the response of the nictitating membrane to pre- and postganglionic stinsulation and to injected epinephrine and acetylcholine and the vasoconstriction produced by lumbar sympathetic stimulation. U-558 produced vasodilation in the perfused denervated hind limb of the dog and was effective in lowering the blood pressure of spinal cats even in the presensce of infused angiotensin II. Smaller doses of U-558 inhibited the effects of epinephrine but did not inhibit the direct effects of acetylcholine on the nictitating membrane. The data indicate that U-558 possesses both alpha-adrenergic blocking and musculotropic depressant activities. It is postulated that both actions of U-558 probably contribute to the hypotensive effects of this compound.