Pharmacological profile of valsartan, a non-peptide angiotensin II type 1 receptor antagonist. 1st communication: antihypertensive effects of valsartan in hypertensive models.
The antihypertensive effects of valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl¿ valine, CAS 137862-53-4, CGP 48933), an angiotensin II type 1 receptor antagonist, were examined in hypertensive rats and dogs. In normotensive rats and deoxycorticosterone acetate (DOCA)/salt hypertensive rats, valsartan had no effect on blood pressure. Single oral administrations of valsartan at doses of 3-30 mg/kg reduced blood pressure dose-dependently in renal (2 kidney 1 clip, 2K1C) hypertensive and spontaneously hypertensive rats (SHR). Repeated oral administrations of valsartan to these hypertensive rats controlled blood pressure throughout a treatment period of 4 weeks, and showed no rebound phenomenon following drug withdrawal. This drug at 30 mg/kg p.o. decreased blood pressure in renal (2K1C) hypertensive dogs by single and repeated administrations. The extent and duration of the hypotensive action of valsartan were similar to those of enalapril. Valsartan would thus appear as useful as enalapril.
Yamamoto
S
S
Drug Discovery Research Unit, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Hayashi
N
N
Kometani
M
M
Nakao
K
K
Inukai
T
T
D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000633:toxicity; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced; D006977:Hypertension, Renal / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; D003900:Desoxycorticosterone; D000450:Aldosterone; D004656:Enalapril; D000068756:Valsartan; D000803:Angiotensin I; D012083:Renin; D014633:Valine