CARDIOVASCULAR ACTIONS OF GUANCYDINE IN NORMOTENSIVE AND HYPERTENSIVE ANEMALS

¹ Department of Experimental Pharmacology, Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York

In conscious normotensive rats, oral administrations of guancydine caused a dose-related hypotension and bradycardia. Vasopressor responses to angiotensin, renin and phenethylamine were blocked. Responses to epinephrine and norepinephrine were reduced to a lesser degree and responses to vasopressin and BaCl₂ were unaltered. Repeated oral doses of guancydine given to metacorticoid hypertensive rats caused a reduction in both mean blood pressure and cardiac hypertrophy. Guancydine, 8 to 15 mg/kg p.o., produced hypotension in hypertensive (but not normotensive) dogs and had no effect on heart rate. Larger amounts (30 mg/kg) caused hypotension and tachycardia in all types of dogs. This dosage also increased cardiac output in conscious dogs. Vasodilation of the cranial mesenteric and renal vascular beds of anesthetized dogs developed after i.p. injections. Renal vascular resistance also decreased in one conscious dog after p.o. administration. Propranolol partially blocked the hypotensive effects of guancydine. Chronic treatment with guancydine, 80 mg/kg/day, reduced norepinephrine concentrations in the hearts of rats whereas a lesser hypotensive dose (20 mg/kg/day) and an acute dose (100-200 mg/kg) appeared to be without effect.