Kato Tomohiro, Nasu Tetsuo, Sonoda Hiroko, Ito Kaoru M, Ikeda Masahiro, Ito Katsuaki
Department of Veterinary Pharmacology and Anatomy, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
J Cardiovasc Pharmacol. 2008 Jan;51(1):18-23. doi: 10.1097/FJC.0b013e318159b01c.
It is suggested that angiotensin II is involved in the pathogenesis of pulmonary hypertension and subsequent right ventricular hypertrophy; therefore, an angiotensin AT1 receptor antagonist could be beneficial for the treatment of this disease. We tested the effect of the new AT1 receptor antagonist olmesartan medoxomil on monocrotaline-induced pulmonary hypertension in rats. At 3 weeks after a single subcutaneous injection of monocrotaline (50 mg/kg), the lung/body weight ratio, the right ventricle/(left ventricle plus septum) weight ratio [RV/(LV+S)], and right ventricular systolic pressure were increased, indicating establishment of pulmonary hypertension and right ventricular hypertrophy. Oral administration of olmesartan medoxomil (2 or 5 mg/kg/day for 3 weeks) restored RV/(LV+S) and right ventricular systolic pressure, and a higher dose (5 mg/kg/day) improved the lung/body weight ratio. Pulmonary arteries isolated from monocrotaline-treated rats exhibited an increase in basal tone in the resting state, indicating that they had intrinsic tone. Three weeks of treatment with olmesartan decreased this intrinsic tone. These data suggest that long-term treatment with olmesartan has beneficial effects on monocrotaline-induced pulmonary hypertension and subsequent right ventricular hypertrophy.
提示血管紧张素II参与肺动脉高压及随后的右心室肥厚的发病机制；因此，血管紧张素AT1受体拮抗剂可能对该病的治疗有益。我们测试了新型AT1受体拮抗剂奥美沙坦酯对大鼠野百合碱诱导的肺动脉高压的作用。单次皮下注射野百合碱（50mg/kg）3周后，肺/体重比、右心室/（左心室加室间隔）重量比[RV/（LV+S）]及右心室收缩压升高，表明肺动脉高压和右心室肥厚形成。口服奥美沙坦酯（2或5mg/kg/天，共3周）可使RV/（LV+S）及右心室收缩压恢复正常，较高剂量（5mg/kg/天）可改善肺/体重比。从野百合碱处理的大鼠分离出的肺动脉在静息状态下基础张力增加，表明其具有内在张力。奥美沙坦治疗3周可降低这种内在张力。这些数据提示，长期使用奥美沙坦对野百合碱诱导的肺动脉高压及随后的右心室肥厚具有有益作用。
