Weber K T, Brilla C G, Campbell S E, Guarda E, Zhou G, Sriram K
Department of Internal Medicine, University of Missouri-Columbia.
Basic Res Cardiol. 1993;88 Suppl 1:107-24. doi: 10.1007/978-3-642-72497-8_8.
In this report we review the replacement (i.e., scarring) and reactive (i.e., perivascular and interstitial fibrosis) fibrous tissue responses found in the myocardium in response to effector hormones of the renin-angiotensin-aldosterone system. Experimental data are presented to indicate: a) endogenous or exogenous elevations in plasma angiotensin II are associated with acute cardiac myocyte necrosis and subsequent microscopic scarring; b) chronic elevations in plasma aldosterone (ALDO), relative to Na+ intake, are associated with a perivascular and interstitial fibrosis of the coronary and systemic circulations and are also seen in response to chronic administration of the mineralocorticoid hormone deoxycorticosterone (DOC); and c) chronic mineralocorticoid excess, due to ALDO or DOC, is associated with enhanced urinary K+ excretion, cardiac myocyte necrosis and scarring. Pharmacologic agents which interfere with these effector hormones (e.g., ACE inhibition and ALDO receptor antagonism) protect the myocardium against this pathologic structural remodeling created by the reactive and replacement (reparative) fibrosis. Evidence is also presented to indicate that chronic ACE inhibition is associated with a regression in reactive myocardial fibrosis. Based on these experimental findings we would suggest that clinical trials are indicated to address the prevention and regression of myocardial fibrosis--an important determinant of pathologic structural remodeling and abnormal myocardial stiffness.
在本报告中，我们回顾了心肌中发现的针对肾素 - 血管紧张素 - 醛固酮系统效应激素的替代性（即瘢痕形成）和反应性（即血管周围和间质纤维化）纤维组织反应。实验数据表明：a）血浆血管紧张素II的内源性或外源性升高与急性心肌细胞坏死及随后的微观瘢痕形成有关；b）相对于钠摄入量，血浆醛固酮（ALDO）的慢性升高与冠状动脉和体循环的血管周围和间质纤维化有关，并且在长期给予盐皮质激素脱氧皮质酮（DOC）时也可见；c）由于ALDO或DOC导致的慢性盐皮质激素过量与尿钾排泄增加、心肌细胞坏死和瘢痕形成有关。干扰这些效应激素的药物（如血管紧张素转换酶抑制和醛固酮受体拮抗）可保护心肌免受由反应性和替代性（修复性）纤维化引起的这种病理性结构重塑。也有证据表明长期血管紧张素转换酶抑制与反应性心肌纤维化的消退有关。基于这些实验结果，我们建议开展临床试验以解决心肌纤维化的预防和消退问题，心肌纤维化是病理性结构重塑和心肌异常僵硬的一个重要决定因素。
