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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670101/
• 关键词: endothelin-1; hypertension; endothelin type-A receptor; endothelin type-B receptor; renal injury; deoxycorticosterone; DOCA食塩高血圧; ETAレセプター; ET_Bレセプター

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

在多种实验性高血压模型中，我们研究了内皮素（ET）在醋酸脱氧皮质酮（DOCA）盐诱导的大鼠高血压和肾损伤发病机制中的作用。DOCA-盐治疗2周后，分别给予选择性ET_A受体拮抗剂ABT-627或选择性ET_B受体拮抗剂A-192621治疗2周，检测大鼠的全身及肾功能指标。ABT-627的每日给药几乎完全消除了高血压和肾功能不全的发展，并显著改善了心血管肥大。肾小球、肾小管及肾小动脉均有病变。相比之下，尽管A-192621不影响DOCA盐诱导的高血压的发展，但该药物使肾功能不全和组织损伤恶化。A-192621可明显促进DOCA盐性高血压的发生发展。这些结果支持了ET_A受体介导的作用在DOCA盐性高血压的发病机制中起重要作用的观点。另一方面，ET_（B）受体介导的抗血管和肾脏损伤的作用也可能在此模型中发挥。我们还发现DOCA盐诱导的高血压大鼠肠系膜动脉对去甲肾上腺素的收缩反应增强。ET_B受体拮抗剂可使这种增强降低到正常血压动物的水平。在DOCA盐诱导的高血压大鼠肠系膜动脉中，局部产生的ET-1可能通过刺激ET_B受体参与上述增强作用。此外，蛋白激酶C系统似乎也参与了这一现象

项目成果

松村靖夫: "高血圧病変の発症と進展におけるエンドセリンETAおよびETB受容体の役割"血管. 22. 53-60 (1999)

Yasuo Matsumura：“内皮素 ETA 和 ETB 受体在高血压病变的发生和进展中的作用”血管。 22. 53-60 (1999)

松村靖夫: "高血圧病変の発症と進展におけるエンドセリンET_AおよびET_B受容体の役割"血管. 22. 53-60 (1999)

Yasuo Matsumura：“内皮素 ET_A 和 ET_B 受体在高血压病变的发生和进展中的作用”血管。 22. 53-60 (1999)

Yasuo Matsumura: "Selective antagonism of endothelin ETA or ETB receptor in renal hemdynamics and function of DOCA-salt induced hypertensive rats"Biol. Pham. Bull. 22. 858-862 (1999)

Yasuo Matsumura：“内皮素 ETA 或 ETB 受体在 DOCA 盐诱导的高血压大鼠肾血流动力学和功能中的选择性拮抗作用”Biol。

KITA Satomi, TANIGUCHI Yuko CHATANI Sumiko and MATSUMURA Yasuo: "Effects of endothelin-1 on norepinephrne-induced vasoconstriction in deoxycorticosterone acetate-salt hypertensive rats"Eur. J. Pharmacol. 344. 53-57 (1998)

KITA Satomi、TANIGUCHI Yuko CHATANI Sumiko 和 MATSUMURA​​ Yasuo：“内皮素-1 对醋酸脱氧皮质酮盐高血压大鼠去甲肾上腺素诱导的血管收缩的影响”Eur。

MATSUMURA Yasuo: "Role of endothelin ETA and ETB receptors in the development of hypertensive diseases"Jpn. J. Circ. Res. 22. 53-60 (1999)

松村康夫：“内皮素ETA和ETB受体在高血压疾病发展中的作用”Jpn。