HYPOTENSIVE ACTION OF PROPRANOLOL AND A NEW BETA-BLOCKING AGENT, D-32 IN CONSCIOUS NORMOTENSIVE AND RENAL HYPERTENSIVE DOGS

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 220  (1) , 4-18
Abstract
The hypotensive action of dl-propranolol and a new .beta.-blocking agent, dl-tert-butylamino-3-(2'', 3''-dimethylphenoxy)-2-propanol hydrochloride (D-32) were studied in conscious normotensive and renal hypertensive dogs, using a cross-over design. The effects were compared with that of placebo (lactose 200 mg/head, orally.) administered in a blind fashion. A marked reduction in systolic blood pressure, from 158 .+-. 2.9 to 124 .+-. 2.3 (mean .+-. S.E.) mm Hg, was observed at 3 h after administration of 50 mg/kg, orally of D-32 in renal hypertensive dogs but not in normotensive ones. In both normotensive and renal hypertensive dogs, 10 and 50 mg/kg, orally of D-32 caused a marked increase in heart rate. I.v. infusion of p-OH D-32, a main metabolite of D-32, in dogs, at a rate of 1 mg/kg per min for 5 min into renal hypertensive dogs caused a significant, long-lasting fall in blood pressure and a sustained increase in heart rate, whereas that of D-32 (1 mg/kg per min for 5 min) failed to do so. Propranolol (10 and/or 50 mg/kg, orally produced no significant changes in blood pressure and heart rate in both preparations. D-32 causes a fall in blood pressure in conscious renal hypertensive dogs mainly by a metabolite of D-32, p-OH D-32.