Cardiovascular effects of orally administered ABBOTT-81988, an angiotensin II antagonist, in conscious spontaneously hypertensive rats

• Published in: American journal of hypertension Vol. 7; no. 11; p. 975
• Main Authors: Lee, J Y, Warner, R B, Brune, M E, Adler, A L, Winn, M, De, B, Zydowsky, T M, Opgenorth, T J, Kerkman, D J, DeBernardis, J F
• Format: Journal Article
• Language: English
• Published: United States 01-11-1994
• Subjects: Administration, Oral; Angiotensin II - antagonists & inhibitors; Animals; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Blood Pressure - drug effects; Heart Rate - drug effects; Hemodynamics - drug effects; Hypertension - drug therapy; Male; Nicotinic Acids - administration & dosage; Nicotinic Acids - pharmacology; Rats; Rats, Inbred SHR; Tetrazoles - administration & dosage; Tetrazoles - pharmacology
• ISSN: 0895-7061
• DOI: 10.1093/ajh/7.11.975

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.