Ishihata Akira, Katano Yumi
Department of Physiology I, Yamagata University School of Medicine, Japan.
Ann N Y Acad Sci. 2006 May;1067:173-81. doi: 10.1196/annals.1354.021.
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.
血管紧张素 II（AII）和内皮素 -1（ET -1）被视为心血管功能随年龄变化的关键因素。已知它们参与心脏纤维化和冠状动脉粥样硬化的发病机制。在老年大鼠Langendorff灌注心脏的冠状动脉中，AII和ET诱导的血管收缩增强。在乳头肌中，ET -1诱导的正性肌力作用（PIE）随衰老而减弱。另一方面，与年轻大鼠相比，ET -1和AII在老年大鼠冠状动脉中引起的血管收缩更强。为了进一步阐明ET -1和AII心血管效应这些年龄依赖性变化的机制，我们检测了年轻（2个月大）和老年（24个月大）大鼠中AII和ET -1受体的表达。从左心室分离总RNA。分别采用竞争性RT -PCR和Northern印迹分析来测定AT(1)受体和ET(A)/ET(B)受体mRNA的基因表达。在左心室膜部分进行[(125)I]ET -1受体测定。与年轻大鼠相比，老年大鼠左心室中AT(1)受体、ET(A)受体和ET(B)受体mRNA上调。ET -1受体的亲和力未改变，但老年大鼠的受体密度显著增加。尽管老年大鼠心脏中AT(1)受体和ET -1受体上调的确切机制尚未阐明，但这些发现表明肾素 -血管紧张素系统以及ET受体的激活可能对老年心脏的生理变化很重要。
