Yamamoto S, Hayashi N, Kometani M, Nakao K, Inukai T
Drug Discovery Research Unit, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Arzneimittelforschung. 1997 May;47(5):604-12.
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.
对血管紧张素II 1型受体拮抗剂缬沙坦（(S)-N-戊酰基-N-[[2'-(1H-四氮唑-5-基)联苯-4-基]甲基]缬氨酸，CAS 137862-53-4，CGP 48933）在高血压大鼠和犬中的降压作用进行了研究。在正常血压大鼠和醋酸脱氧皮质酮（DOCA）/盐性高血压大鼠中，缬沙坦对血压无影响。在肾性（两肾一夹，2K1C）高血压大鼠和自发性高血压大鼠（SHR）中，单次口服3 - 30 mg/kg剂量的缬沙坦可使血压呈剂量依赖性降低。对这些高血压大鼠重复口服缬沙坦，在整个4周的治疗期间可控制血压，且停药后无反跳现象。该药物以30 mg/kg口服给药，单次和重复给药均可降低肾性（2K1C）高血压犬的血压。缬沙坦降压作用的程度和持续时间与依那普利相似。因此，缬沙坦似乎与依那普利一样有用。
