Basic Research on the vascular renin-angiotensin system

近年来，血管紧张素转换酶（ACE）抑制剂的有效性已得到临床验证，并被视为治疗高血压的一线药物之一。ACE抑制剂的作用机制并不能仅仅通过抑制循环中的肾素-血管紧张素系统或增强激肽释放酶-激肽系统来解释。我们发现血管ACE活性升高与慢性肾性高血压的发生和维持密切相关。此后，血管肾素-血管紧张素系统的生理和病理生理重要性已被认识，但血管组织中血管紧张素I的产生机制仍不清楚。在本研究中，首先，通过测量双侧肾切除大鼠血浆和血管肾素活性（血管紧张素I产生对抗肾素抗体敏感的活性）的变化，以生化方式证明血管肾素的可能存在。血管肾素活性也被检测到， 关于我们 在非病理条件下的人胃网膜动脉。此外，在有内皮的人动脉中的肾素活性显著高于无内皮的人动脉，表明血管内皮中存在肾素。其次，血管肾素用抗人重组肾素抗体用改良的亲和素-生物素-过氧化物酶复合物法进行免疫化学染色;阳性染色选择性地发生在内皮细胞中。这些结果表明，在生理条件下，肾素存在于动脉内皮细胞中。不能确定肾素是被内皮细胞摄取还是在细胞中合成。然而，在任何情况下，我们得出结论，血管内皮细胞中可能产生血管紧张素I。血管内皮细胞在高血压和动脉粥样硬化的发生、发展和维持中起着重要作用。目前对血管肾素-血管紧张素系统的研究强调了内皮功能在调节血管张力和平滑肌细胞增殖中的重要性。少

Recently, effectiveness of angiotensin-converting enzyme (ACE) inhibitors has been clinically validated and regarded as one of the first-line drugs for the treatment of hypertension. Mechanisms of action of ACE inhibitors have not solely been explained by inhibition of circulating renin-angiotensin system or potentiation of kallikrein-kinin system. We found that elevation of vascular ACE activity is closely related to the development and maintenance of chronic renal hypertension. Thereafter, the physiological and pathophysiological importance of vascular renin-angiotensin system has been recognized, but mechanism of angiotensin I generation in the vascular tissues remained unknown. In the present study, firstly, possible existence of vascular renin was biochemically demonstrated by measuring alterations in plasma and vascular renin activity (angiotensin I generating activity sensitive to antirenin antibody) in bilaterally nephrectomized rats. Vascular renin activity was detected also i … More n human gastroepiploic arteries under non-pathological conditions. Further, renin activity in human arteries with endothelium was significantly higher than in those without endothelium, suggesting the existence of renin in the vascular endothelium. Secondly, vascular renin was immunohistochemically stained using a modified avidine-biotin-peroxidase complex method with anti-human recombinant renin antibody; positive staining selectively occurred in the endothelial cells. These results suggest that renin is present in endothelial cells of arteries under physiological conditions. Whether renin is taken up by the endothelial cells or synthesized in the cells could not be determined. However, in any event, We concluded a possible generation of angiotensin I in the vascular endothelium. It has been suggested that vascualar endothelium plays an important role in the initiation, development and maintenance of hypertension and atherosclerosis. The present study on the vascular renin -angiotensin system emphasizes the importance of endothelial function in the regulation of vascular tone and smooth muscle cell proliferation. Less