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

Angiotensin II (All) 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. All- 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 All 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 All, we examined the expression of All 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 AT) receptor and ET A /ET B receptor mRNA, competitive RT-PCR and Northern blot analysis were performed, respectively. [ 1 2 5 I]ET-1 receptor assay was carried out in left ventricular membrane fraction. AT 1 -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 AT 1 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.