Isoproterenol-induced impairment of heart function and remodeling are attenuated by the nonpeptide angiotensin-(1-7) analogue AVE 0991
Isoproterenol-induced impairment of heart function and remodeling are attenuated by the nonpeptide angiotensin-(1-7) analogue AVE 0991
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DOI：
10.1016/j.lfs.2007.07.022
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发表时间：
2007-08-23
期刊：
影响因子：
6.1
通讯作者：
Santos, Robson A. S.
中科院分区：
文献类型：
--
作者：
Ferreira, Anderson J.;Oliveira, Thauana L.;Santos, Robson A. S.
本研究的目的是评价AVE 0991（AVE），一种模拟Ang-（1-7）作用的非肽类化合物，对心脏重塑的影响。用异丙肾上腺素（ISO）（2 mg/kg i. p./ 7天）。在7天期结束时，根据Langendorff方法对心脏进行灌注以评价心功能。记录心脏、心房和右心室和左心室湿重，针对体重进行标准化，然后表示为肌肉质量指数（mg/g）。此外，用苏木精-伊红对左心室连续切片进行细胞形态学染色，并用胶原特异性Masson三色法检测纤维化。免疫荧光标记和共聚焦显微镜被用来调查的分布和沉积的胶原蛋白类型I，III，VI，和纤连蛋白。AVE减少ISO诱导的肥大，如通过肌细胞直径测量所定量的（对照：10.60 +/- 0.08 μ m; ISO：14.60 +/- 0.11 μ m; ISO+AVE：11.22 +/- 0.08 μ m，n = 5）。此外，AVE还能明显抑制ISO引起的细胞外基质蛋白的增加。AVE处理还减弱了ISO引起的收缩张力和+/- dT/dt的降低，并加重了ISO引起的血管舒张。这些结果表明，AVE对ISO诱导的心脏重构具有心脏保护作用。(C)2007年爱思唯尔公司All rights reserved.
The aim of this study was to evaluate the effects of AVE 0991 (AVE), a nonpeptide compound that mimics Ang-(1-7) actions, on cardiac remodeling. Heart hypertrophy and heart dysfunction were induced by isoproterenol (ISO) (2 mg/kg i.p./day for 7 days) in male Wistar rats. At the end of the 7-day period, the hearts were perfused according to the Langendorff method to evaluate cardiac function. The hearts, atria, and right and left ventricles wet weights were recorded, normalized for body weight and then expressed as muscle mass index (mg/g). In addition, serial sections from left ventricle were stained with hematoxylin-eosin for cell morphometry and with collagen-specific Masson's trichrome for detection of fibrosis. Immunofluorescence-labeling and confocal microscopy were used to investigate the distribution and deposition of collagen types I, III, VI, and fibronectin. AVE reduced the ISO-induced hypertrophy as quantified by myocyte diameter measurements (Control: 10.60 +/- 0.08 mu m; ISO: 14.60 +/- 0.11 mu m; ISO+AVE: 11.22 +/- 0.08 mu m, n = 5). In addition, AVE markedly attenuated the increase of extracellular matrix proteins induced by ISO. AVE treatment also attenuated the decrease in systolic tension and +/- dT/dt and exacerbated the vasodilatation induced by ISO. These results show that AVE has a cardioprotective effect on ISO-induced cardiac remodeling. (C) 2007 Elsevier Inc. All rights reserved.