Hypotensive action of propranolol and a new beta-blocking agent, D-32 in conscious normotensive and renal hypertensive dogs.
The hypotensive actions 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, p.o.) 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 hr after administration of 50 mg/kg, p.o. of D-32 in renal hypertensive dogs but not in normotensive ones. In both normotensive and renal hypertensive dogs, 10 and 50 mg/kg, p.o. of D-32 caused a marked increase in heart rate. Intravenous 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, p.o.) produced no significant changes in blood pressure and heart rate in both preparations. These results indicate that D-32 causes a fall in blood pressure in conscious renal hypertensive dogs mainly by a metabolite of D-32, p-OH D-32.
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003864:Depression, Chemical; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000503:physiopathology*; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011433:Propranolol