ABBOTT-81988 (A-81988), 2-(N-propyl-N[(2'-[1H-tetrazol-5-yl]
biphenyl- 4yl)methyl] amino) pyridine-3-carboxylic
acid, a nonpeptide
angiotensin II (AII) antagonist was studied in the conscious spontaneously hypertensive rate (SHR) (male, 18 to 21 weeks) for cardiovascular effects of
oral administration. Oral
A-81988 at 0.3 to 3 mg/kg produced a dose-related 10 to 29% decrease in mean arterial pressure (MAP) in SHR (control, 161 to 177 mm Hg; n = 19) for 12 to 24 h without changing heart rate. Oral
A-81988 at 3 mg/kg daily maintained MAP in SHR at normotensive levels (97 to 120 mm Hg) during a 5-day protocol with no rebound
hypertension at termination of treatment. There was an increase in plasma
renin activity in nanograms AI/milliliter/hour in SHR treated with
A-81988 (32 +/- 3, n = 6 v 5 +/- 2, n = 6 for vehicle) during its
antihypertensive action. The oral potency of
A-81988 was enhanced about 10-fold in
furosemide-treated SHR. The pressor response to AII was inhibited selectively in SHR even after an 8-day treatment with
A-81988 (approximately 3 mg/kg/day orally). Total peripheral resistance was lowered and cardiac output unchanged in SHR administered
A-81988 (3 mg/kg/day orally for 2 days).
A-81988 (3 mg/kg orally) did not cause
orthostatic hypotension in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)