Cardiovascular effects of GR117289, a novel angiotensin AT1 receptor antagonist

• Published in: British journal of pharmacology 1994-01, Vol.111 (1), p.137-144
• Main Authors: Hilditch, A., Hunt, A.A.E., Gardner, C.J., Twissell, D.J., Polley, J., Travers, A., Drew, G.M., Middlemiss, D., Ross, B.C., Robertson, M.J.
• Format: Article
• Language: English
• Subjects: Administration, Oral; angiotensin AT1 receptor antagonist; angiotensin AT1 receptors; Angiotensin II - pharmacology; angiotensin pressor responses; Angiotensin Receptor Antagonists; Animals; blood pressure; Blood Pressure - drug effects; Callithrix; conscious dog; conscious marmoset; Conscious rat; Dogs; Dose-Response Relationship, Drug; GR 117289; Hypertension - drug therapy; Hypertension - physiopathology; Hypertension, Renovascular - drug therapy; Hypertension, Renovascular - physiopathology; hypertensive rat models; Injections, Intra-Arterial; Male; Nicotinic Acids - administration & dosage; Nicotinic Acids - pharmacology; Nicotinic Acids - therapeutic use; Rats; Rats, Inbred SHR; Tetrazoles - administration & dosage; Tetrazoles - pharmacology; Tetrazoles - therapeutic use
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1994.tb14035.x

1 The effect of GR117289, an angiotensin AT1 receptor antagonist, on diastolic blood pressure (DBP) was determined in angiotensin‐dependent and angiotensin‐independent models of hypertension in rats. In addition, the antagonist profile of GR117289 at angiotensin AT1 receptors was determined in conscious renal hypertensive rats and conscious normotensive rats, dogs and marmosets. 2 Intra‐arterial and oral administration of GR117289 (0.3–3 mg kg−1, i.a.; 1–10 mg kg−1, p.o.) to 6‐day left renal artery ligated hypertensive (RALH) rats (DBP > 140 mmHg) produced significant, dose‐related reductions in DBP with little apparent effect on heart rate (