QUINAPRIL DECREASES MYOCARDIAL ACCUMULATION OF EXTRACELLULAR-MATRIX COMPONENTS IN SPONTANEOUSLY HYPERTENSIVE RATS

被引：54

作者：

PANIZO, A ^{[1
]}

PARDO, J ^{[1
]}

HERNANDEZ, M ^{[1
]}

GALINDO, MF ^{[1
]}

CENARRUZABEITIA, E ^{[1
]}

JAVIER, D ^{[1
]}

机构：

[1] FAC MED PAMPLONA,DEPT MED INTERNA,UNIDAD FISIOPATOL VASC,E-31080 PAMPLONA,SPAIN

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1995年 / 8卷 / 08期

关键词：

ARTERIAL HYPERTENSION; EXTRACELLULAR MATRIX; MYOCARDIAL REMODELING; QUINAPRIL;

D O I：

10.1016/0895-7061(95)00120-E

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

In genetic and acquired hypertension, a structural remodeling of the nonmyocyte compartment of myocardium, including the accumulation of fibrillar collagen and other components of the extracellular matrix (ECM) within the interstitium, represents a determinant of pathologic hypertrophy that leads to ventricular dysfunction. Therefore, to evaluate the potential benefit of the angiotensin converting enzyme (ACE) inhibitor quinapril in reversing the interstitial remodeling in spontaneously hypertensive rats (SHR) with established left ventricular hypertrophy (LVH), we treated 16-week-old male SHR with oral quinapril (average dose, 10 mg/kg body weight/day) for 20 weeks. Interstitial fibrosis was determined morphometrically using an automatic image analyzer. The amount of collagen was evaluated by measuring; myocardial hydroxyproline concentration. Myocardial deposition of collagen molecules (types I, III, and IV) and other ECM components (fibronectin, laminin) was analyzed by immunohistochemical techniques using specific monoclonal antibodies. The activity of ACE was measured in left ventricular tissue by a fluorometric assay. In quinapril-treated SHR compared with 36-week-old untreated SHR and age- and sex-matched Wistar-Kyoto (WKY) controls, we found 1) a lesser degree of LVH and a lesser level of blood pressure, 2) a lesser degree of interstitial fibrosis, represented by less interstitial collagen volume fraction (5.73 +/- 0.45% v 3.42 +/- 0.28%, P < .05; WKY, 3.44 +/- 0.66%), 3) a lower hydroxyproline concentration (1.09 +/- 0.05 mu mol/L/g dry weight/100 g body weight to 0.81 +/- 0.05 mu mol/L/g dry weight/100 g body weight, P < .05; WKY, 0.96 +/- 0.06 mu mol/L/g dry weight/100 g body weight), 4) a lesser presence of collagen fibers, and 5) a lesser presence of collagen IV, fibronectin, and laminin, The activity of cardiac ACE was inhibited by 36% in quinapril-treated SHR as compared with 36-week-old untreated SHR. These results indicate that quinapril reversed fibrosis in SHR with LVH and adverse structural remodeling of the cardiac interstitium. This was associated with a decrease in the presence of ECM components in the myocardium. These cardioreparative properties of quinapril can be valuable in preventing left ventricular dysfunction in hypertensive heart disease.

引用

页码：815 / 822

页数：8

共 27 条

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