Nakamoto Takaaki, Harasawa Hiroshi, Akimoto Kazumi, Hirata Hisato, Kaneko Hiromichi, Kaneko Noboru, Sorimachi Kenji
Department of Cardiology and Pneumology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Eur J Pharmacol. 2005 Dec 28;528(1-3):43-51. doi: 10.1016/j.ejphar.2005.10.063. Epub 2005 Dec 5.
We established a rat chronic alveolar hypoxia in vivo model to evaluate the efficacy against hypoxic pulmonary hypertension of a new angiotensin II-receptor I blocker, olmesartan medoxomil. Three groups of rats were established: rats exposed for 2-6 weeks to 10% oxygen atmosphere in a normobaric chamber; hypoxic rats treated with olmesartan medoxomil oral administration (5 mg/day) every day; and control rats fed in a normoxic condition. After hypoxia treatment, the presence, etiology and severity of pulmonary hypertension, was echocardiographically evaluated, and expressions of brain natriuretic peptide (BNP), transforming growth factor (TGF-beta) and endothelin-1 genes measured by both immunohistochemical assay and real-time polymerase chain reaction. Olmesartan medoxomil significantly reduced the induction of hypoxic cor pulmonale not only on echocardiographical observations but also in BNP, TGF-beta and endothelin gene expressions in molecular studies. However, systolic blood pressure was independent of olmesartan medoxomil. The present study clearly indicates that the angiotensin II-type I-receptor blocker olmesartan medoxomil has significant efficacy for hypoxic cor pulmonale.
我们建立了大鼠慢性肺泡低氧体内模型，以评估新型血管紧张素II受体I阻滞剂奥美沙坦酯对低氧性肺动脉高压的疗效。将大鼠分为三组：在常压舱中暴露于10%氧气环境2 - 6周的大鼠；每天口服奥美沙坦酯（5毫克/天）的低氧大鼠；以及在常氧条件下饲养的对照大鼠。低氧处理后，通过超声心动图评估肺动脉高压的存在、病因和严重程度，并通过免疫组织化学分析和实时聚合酶链反应测量脑钠肽（BNP）、转化生长因子（TGF-β）和内皮素-1基因的表达。在超声心动图观察以及分子研究中BNP、TGF-β和内皮素基因表达方面，奥美沙坦酯均显著降低了低氧性肺心病的诱发。然而，收缩压不受奥美沙坦酯影响。本研究清楚地表明，血管紧张素II 1型受体阻滞剂奥美沙坦酯对低氧性肺心病具有显著疗效。
