LEFT-VENTRICULAR FIBROSIS IN RENOVASCULAR HYPERTENSIVE RATS - EFFECT OF LOSARTAN AND SPIRONOLACTONE
LEFT-VENTRICULAR FIBROSIS IN RENOVASCULAR HYPERTENSIVE RATS - EFFECT OF LOSARTAN AND SPIRONOLACTONE
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DOI：
10.1161/01.hyp.26.1.101
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发表时间：
1995-07-01
期刊：
影响因子：
8.3
通讯作者：
MICHEL, JB
中科院分区：
文献类型：
--
作者：
NICOLETTI, A;HEUDES, D;MICHEL, JB
动脉高血压引起的心肌纤维化改变了心肌的结构和功能。心肌纤维化的特点是I型和III型胶原的病理性堆积。我们使用一种醛固酮拮抗剂(螺内酯)和一种血管紧张素II拮抗剂(氯沙坦)来阐明这两种激素和高血压在两肾一夹高血压Goldblatt模型大鼠心肌纤维化形成中的作用。在间质间隙、冠状动脉周围、微小疤痕区域和天狼星红染色的左心室切片上用计算机辅助形态计量学和生化技术评估纤维化。用标准光显微镜和偏光显微镜进行形态测量；后一种方法被用来定量黄红色和绿色的胶原纤维。同时，用半定量聚合酶链式反应方法检测I型和III型胶原mRNAs的表达。未治疗的两肾一夹高血压大鼠心肌胶原含量增加，主要分布在冠状动脉周围；慢性高血压大鼠微瘢痕的数量和表面积也有所增加。氯沙坦治疗降低了所有区域的收缩压和黄红色胶原纤维含量，而螺内酯治疗降低了绿色胶原纤维含量，但没有降低收缩压。I型和III型胶原的mRNA表达水平分别与黄红色和绿色胶原纤维的含量相似，提示黄红色胶原纤维主要为I型胶原纤维，绿色胶原纤维主要为III型胶原纤维。这些结果表明，血管紧张素II可能与高血压一起，以及不依赖高血压的醛固酮对心肌纤维化有重要影响，分别诱导I型和III型胶原沉积，主要分布在冠状动脉周围。
Myocardial fibrosis resulting from arterial hypertension alters myocardial structure and function. Myocardial fibrosis is characterized by a pathological accumulation of types I and III collagens. We used an aldosterone antagonist (spironolactone) and an angiotensin II antagonist (losartan) to elucidate the respective role of these hormones and hypertension in the development of myocardial fibrosis in the Goldblatt model of two-kidney, one clip hypertension in the rat. Fibrosis was assessed by computer-assisted morphometry in the interstitial space, around coronary arteries, in microscar areas, and on left ventricular sections stained with Sirius red and by biochemical techniques. Morphometry was performed with both standard light and polarization microscopy; this latter method was used to quantify yellow-red and green collagen fibers. Concurrently, type I and type III collagen mRNAs were evaluated by a semiquantitative polymerase chain reaction method. The collagen content of the untreated two-kidney, one clip hypertensive rats increased mainly around the coronary arteries; the number and surface area of microscars also increased in chronic hypertension. Losartan treatment decreased systolic pressure and yellow-red collagen fiber content in all areas, whereas spironolactone treatment decreased green collagen fiber content without decreasing systolic pressure. mRNA levels for types I and III collagens showed profiles similar to those of yellow-red and green collagen fiber contents, respectively, suggesting that yellow-red collagen fibers are mainly type I collagen fibers and green collagen fibers are mainly type III collagen fibers. These results suggest that angiotensin II, possibly together with hypertension, and aldosterone, independently of hypertension, have a major influence on myocardial fibrosis, inducing type I and type III collagen deposits, respectively, mainly around coronary arteries.