Role of endothelin-1 in the yenal injury of hypertension

内皮素1在高血压肾损伤中的作用

基本信息

批准号：
10670101
负责人：
MATSUMURA Yasuo
金额：
$ 1.54万
依托单位：
Osaka University of Pharmaceutical Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Among various experimental hypertensive models, we investigated the involvement of endothelin (ET) in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt-induced hypertesion and renal injury in rats. Two weeks after the start of DOCA-salt treatment, the rats were given ABT-627, a selective ET\A receptor antagonist or A-192621, a selective ET_B receptor antagonist for 2 weeks, and their systemic and renal functional parameters were examined. The dily administration of ABT-627 almost completely abolished the development of hypertension and renal dysfunction, and markedly improved the cardiovascular hypertrophy. There were nolesions in glomeruli, tubles and renal small arteries. In contrast, althouth A-192621 did not affect the development of DOCA-salt-induced hypertension, renal dysfunction and tissue injury were deteriorated by this agent. The develpoment of cardiovascular hypertrophy was significantly enhanced by A-192621.These results strongly support the view thet ET_A receptormediated action plays an important role in the pathogenesis of DOCA-salt-induced hypertension. On the other hand, it seems likely that hte ET_B receptor-mediated action protects against vascular and renal injuries, in this model of hypertensionWe also found that the contractile responses to noreinephrine were enhanced in mesenteric arteries of DOCA-salt-induced hypertensive rats. This enhancement was declined to the level seen with normotensive animals by ET_B receptor antagonist. Thus, in mesenteric arteries of DOCA-salt-induced hypertensive rats, locally generated ET-1 may contribute to the above enhancement via stimulation of ET_B receptor. In addition, the protein kinase C system seems to be involved in this phenomenon

在各种实验性高血压模型中，我们研究了内皮素（ET）参与大鼠乙酸脱氧核心酮（DOCA） - 大鼠中的高血压和肾损伤。 DOCA盐处理开始后的两周，将大鼠ABT-627，选择性ET \ A受体拮抗剂或A-192621，选择性ET_B受体拮抗剂2周，并检查其系统性和肾功能参数。 ABT-627的Dily给药几乎完全消除了高血压和肾功能障碍的发展，并显着改善了心血管肥大。肾小球，tubles和肾小管有诺尔斯。相比之下，Althouth A-192621不会影响DOCA盐引起的高血压，肾功能障碍和组织损伤的发展。 A-192621显着增强了心血管肥大的开发性。这些结果强烈支持Thet ET_A受体介导的作用在DOCA-SALT诱导的高血压的发病机理中起重要作用。另一方面，HTE ET_B受体介导的作用似乎可以预防血管和肾脏损伤，在这种高血压模型中还发现，在DOCA-SALT诱导的高血压高度大鼠的肠系膜动脉中，对去甲肾上腺素的收缩反应得到了增强。 ET_B受体拮抗剂对正常动物看到的水平降低了这种增强。因此，在DOCA盐诱导的高血压大鼠的肠系膜动脉中，局部生成的ET-1可能通过刺激ET_B受体有助于上述增强。此外，蛋白激酶C系统似乎参与了这种现象