Role of Angiotensin II and Endothelin-1 Receptors in Aging-Related Functional Changes in Rat Cardiovascular System

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Abstract

ABSTRACT

Angiotensin II (AII) and endothelin-1 (ET-1) are regarded as key players in the age-related changes in cardiovascular function. They are known to be involved in the pathogenesis of cardiac fibrosis and coronary vascular atherosclerosis. AII- and ET-induced vasoconstriction was augmented in coronary arteries of Langendorff-perfused heart from aged rats. In papillary muscles, ET-1-induced positive inotropic effect (PIE) was diminished by aging. On the other hand, both ET-1 and AII caused greater vasoconstriction in aged rat coronary arteries compared to those in the young rat. To further elucidate the mechanism of these age-dependent changes in cardiovascular effects of ET-1 and AII, we examined the expression of AII and ET-1 receptors in young (2-month-old) and aged (24-month-old) rats. Total RNA was isolated from left ventricles. For determination of the gene expression of AT1 receptor and ETA/ETB receptor mRNA, competitive RT-PCR and Northern blot analysis were performed, respectively. [125I]ET-1 receptor assay was carried out in left ventricular membrane fraction. AT1-receptor, ETA-, and ETB-receptor mRNA were upregulated in the left ventricles of senescent rats compared with young ones. The affinity of ET-1-receptor was not changed, but receptor density was significantly increased in aged rats. Although the precise mechanism for the upregulation of AT1 receptor and ET-1 receptor in the aged rat heart has not been clarified yet, these findings suggest that the activation of the renin–angiotensin system as well as ET receptor may be important for the physiological changes in aged hearts.

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