Role of angiotensin II receptor on organ damage and renin angiotensin system

血管紧张素II受体对器官损伤及肾素血管紧张素系统的作用

• 批准号: 05670100
• 负责人: IWAO Hiroshi
• 金额: $ 1.41万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670100/
• 关键词: Angiotensin; Receptor; Heart; Kidney; Blood pressure; Angiotensin II receptor antagonist; Organ damages; TGF-beta1; ECM; Phenotype

Accumulating evidence indicated that transforming-beta1 and extracellular matrix components may be responsible for cardiovascular injury. The increase in collagen matrices in the heart enhances organ stiffness and results in left ventricular diastolic dysfunction, which finally contributes to cardiac failure. Pathological left ventricular hypertrophy, by pressure overload, is accompanied not only by the quantitative change (myocyte hypertrophy) but also by the qualitative changes, including the shift to fetal phenotype of myocytes and interstitial fibrosis. Recent investigation, using cultured cells from the neonatal rat heart, show that angiotensin II in vitro directly causes hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts via AT1 receptor, and that angiotensin II in vitro induces fetal phenotype of genes in cardiac myocytes via AT1 receptor. In this study show that cardiac AT1 receptor in vivo play a critical role in left ventricular hypertrophy, myocardial phenotypic change and interstitial collagen expression of hypertension. The improvement of hypertension-induced left ventricular hypertrophy and molecular changes by AT1 receptor antagonist may be at least in part mediated by its direct action, independent of its hypertensive effect.

越来越多的证据表明，转化-β1和细胞外基质成分可能与心血管损伤有关。心脏中胶原基质的增加增加了器官的硬度，导致左室舒张功能障碍，最终导致心力衰竭。病理性左心室肥厚不仅伴随着心肌细胞肥大的量变(心肌细胞肥大)，还伴随着心肌细胞向胎儿型转化和间质纤维化的质变。最近利用培养的新生大鼠心脏细胞进行的研究表明，血管紧张素II在体外通过AT1受体直接导致心肌细胞肥大和心脏成纤维细胞增殖，并通过AT1受体在体外诱导心肌细胞基因的胎儿表型。本研究表明，心脏AT1受体在高血压左室肥厚、心肌表型改变和间质胶原表达中起重要作用。AT1受体拮抗剂改善高血压所致的左心室肥厚及分子变化，可能至少部分是通过其直接作用而实现的，而不依赖于其升压作用。

项目成果

S.Kim 他: "AT1 receptor-mediated stimulation by angiotensin II of rat aortic fibronectin gene expression in vivo" Br.J.Pharmacol.113. 662-663 (1994)

S. Kim 等人：“AT1 受体介导的血管紧张素 II 对大鼠主动脉纤连蛋白基因表达的体内刺激”Br.J.Pharmacol.113 (1994)。

Akinori Hamaguchi, Shokei Kim, Kensuke Ohta, Keiko Yagi, Tokihito Yukimura, Katsuyuki Miura, Taneo Fukuda, Hirohsi Iwao: "Transforming growth factor-b1 expression and phenotype modulation in the kidney of hypertensive rats" Hypertension. 26. 199-207 (1995

Akinori Hamaguchi、Shokei Kim、Kensuke Ohta、Keiko Yagi、Tokihito Yukimura、Katsuyuki Miura、Taneo Fukuda、Hirohsi Iwao：“高血压大鼠肾脏中转化生长因子-b1 的表达和表型调节”。

Kensuke Ohta, Shokei Kim, Hideki Wanibuchi, Detlev Ganten, Hiroshi Iwao: "Contribution of local renin-angiotensin system to cardiac hypertrophy, phenotypic modulation and remodeling in TGR (mRen2) 27 transgenic rats" Circulation. (in press).

Kensuke Ohta、Shokei Kim、Hideki Wanibuchi、Detlev Ganten、Hiroshi Iwao：“局部肾素-血管紧张素系统对 TGR (mRen2) 27 转基因大鼠心脏肥大、表型调节和重塑的贡献”循环。

Shokei Kim, Kensuke Ohta, Akinori Hamaguchi, Tokihito Yukimura, Katsuyuki Miura, Hiroshi Iwao: "Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats" Hypertension. 25. 1252-1259 (1995)

Shokei Kim、Kensuke Ohta、Akinori Hamaguchi、Tokihito Yukimura、Katsuyuki Miura、Hiroshi Iwao：“血管紧张素 II 在大鼠体内诱导心脏表型调节和重塑”高血压。

S.Kim 他: "Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats" Hypertension. 25. 1252-1259 (1995)

S. Kim 等人：“血管紧张素 II 在大鼠体内诱导心脏表型调节和重塑”高血压。 25. 1252-1259 (1995)