Nicoletti A, Heudes D, Hinglais N, Appay M D, Philippe M, Sassy-Prigent C, Bariety J, Michel J B
Unité 430 INSERM, Hôpital Broussais, Paris, France.
Hypertension. 1995 Jul;26(1):101-11. doi: 10.1161/01.hyp.26.1.101.
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.
动脉高血压导致的心肌纤维化会改变心肌结构和功能。心肌纤维化的特征是I型和III型胶原蛋白的病理性积聚。我们使用醛固酮拮抗剂（螺内酯）和血管紧张素II拮抗剂（氯沙坦）来阐明这些激素以及高血压在大鼠双肾单夹高血压Goldblatt模型中心肌纤维化发展过程中的各自作用。通过计算机辅助形态测量法评估间质空间、冠状动脉周围、微瘢痕区域以及用天狼星红染色的左心室切片中的纤维化情况，并采用生化技术进行评估。形态测量使用标准光学显微镜和偏振显微镜；后一种方法用于量化黄红色和绿色胶原纤维。同时，通过半定量聚合酶链反应法评估I型和III型胶原mRNA。未经治疗的双肾单夹高血压大鼠的胶原含量主要在冠状动脉周围增加；慢性高血压时微瘢痕的数量和表面积也增加。氯沙坦治疗可降低所有区域的收缩压和黄红色胶原纤维含量，而螺内酯治疗可降低绿色胶原纤维含量但不降低收缩压。I型和III型胶原的mRNA水平分别显示出与黄红色和绿色胶原纤维含量相似的变化趋势，这表明黄红色胶原纤维主要是I型胶原纤维，绿色胶原纤维主要是III型胶原纤维。这些结果表明，血管紧张素II可能与高血压共同作用，而醛固酮独立于高血压，对心肌纤维化有重大影响，分别诱导I型和III型胶原沉积，主要在冠状动脉周围。
