Hayashi N, Fujimura Y, Yamamoto S, Kometani M, Nakao K
Drug Discovery Research Unit, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Arzneimittelforschung. 1997 May;47(5):625-9.
The hemodynamic effects of valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)bipheneoyl-4-yl]meth yl¿valine, CAS 137862-53-4, CGP 48933), a new angiotensin II type 1 receptor antagonist, on rats with myocardial infarction induced by coronary artery ligation was examined. Four weeks after ligation, mean blood pressure, left ventricular pressure and cardiac output decreased, while left ventricular end-diastolic pressure increased in control rats. Left ventricular end-diastolic pressure significantly decreased in rats treated with valsartan at 30 mg/kg/d p.o. for 4 weeks. Total systemic resistance remarkably decreased in those with enalapril 3 mg/kg/d p.o. and valsartan 30 mg/kg/d p.o. Valsartan and enalaprilat did not affect cardiac functions of isolated intact rat hearts before and after ischemia in Langendorff apparatus. In addition to hemodynamic effects observed in vivo, valsartan at 30 mg/kg p.o. significantly inhibited left ventricular hypertrophy. Valsartan would thus appear to be clinically useful for treating heart failure following myocardial infarction.
研究了新型血管紧张素II 1型受体拮抗剂缬沙坦（(S)-N-戊酰基-N-¿[2'-(1H-四氮唑-5-基)联苯甲酰-4-基]甲基¿缬氨酸，CAS 137862-53-4，CGP 48933）对冠状动脉结扎诱导的心肌梗死大鼠的血流动力学影响。结扎四周后，对照大鼠的平均血压、左心室压力和心输出量降低，而左心室舒张末期压力升高。口服缬沙坦30 mg/kg/d持续4周的大鼠，其左心室舒张末期压力显著降低。口服依那普利3 mg/kg/d和缬沙坦30 mg/kg/d的大鼠，其总全身阻力显著降低。在Langendorff装置中，缬沙坦和依那普利拉对缺血前后的离体完整大鼠心脏的心脏功能均无影响。除了在体内观察到的血流动力学效应外，口服30 mg/kg缬沙坦还能显著抑制左心室肥厚。因此，缬沙坦在临床上似乎可用于治疗心肌梗死后的心力衰竭。
