Role of angiotensin II and endothelin-1 receptors in aging-related functional changes in rat cardiovascular system.
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 AT(1) receptor and ET(A)/ET(B) receptor mRNA, competitive RT-PCR and Northern blot analysis were performed, respectively. [(125)I]ET-1 receptor assay was carried out in left ventricular membrane fraction. AT(1)-receptor, ET(A)-, and ET(B)-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.
Ishihata
Akira
A
Department of Physiology I, Yamagata University School of Medicine, Japan. ishihata@med.id.yamagata-u.ac.jp
Katano
Yumi
Y
D000375:Aging; D000804:Angiotensin II / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism*; D015870:Gene Expression; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D044022:Receptor, Endothelin A / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D044022:Receptor, Endothelin A; D000804:Angiotensin II