Pathological role of endothelin ET_B receptors

内皮素ET_B受体的病理作用

• 批准号: 12670098
• 负责人: MATSUMURA Yasuo
• 金额: $ 2.18万
• 依托单位: Osaka University of pharmaceutical Sciences, Assistant
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670098/
• 关键词: endothelin-1; ET_B receptor; hypertension; renal failure; 腎障害

We evaluated the pathological role of ET_B receptors in DOCA-salt-induced hypertension, cardiovascular hypertrophy and renal damage, using the spotting-lethal (sl) rat which carries a naturally occurring deletion in ET_B receptor gene. When homozygous (sl/sl) and wild-type (+/+) rats were treated with DOCA-salt, homozygous rats exhibited earlier and higher increases in systolic blood pressure than wild-type rats. Chronic treatment with ABT-627, an ET_A receptor antagonist, completely suppressed DOCA-salt-induced hypertension in both groups. Renal dysfunction and histologial damage were more severe in homozygous than in wild-type rats. Marked vascular hypertrophy was observed in homozygous, compared with wild-type rats. Renal and vaslcular injuries were significantly improved by ABT-627. In DOCA-salt-induced hypertension. Enhanced ET-1 production and ET_A-mediated actions are responsible for the increased susceptivity to DOCA-salt hypertention and tissue injuries in ET_B receptor-defici … More ent ratsUsing same animals, we also evaluated the role of endothelin ET\B-receptor-mediated action in the development and maintenance of ischemic acute renal failure (ARF). Animals were subjected to ischemic ARF by clamping the renal pedicle for 45 min followed by reperfusion. At 24 h after the reperfusion, renal glomerular dysfunction and histological damage were markedly and equally observed both in homozygous and wild-type groups, and these renal njury gradually recovered. When the ischemia/reperfusion-induced renal injury was examined at 7 days after the reperfusion, the recovery in homozygous ARF rats obviously delayed compared with the cases in wild-type animals. Increment of renal endothelin-1 content after the ischemia/reperfusion was more marked in homozygous than in wild-type rats. Thus, ET_B-receptor-mediated actoins do not play an important role in the development of ischemic ARF, but may be involoved in the recovery process from the ischemia/reperfusion-induced renal injury Less

我们评估了ET_B受体在doca-盐 - 叶片，心血管肥大和肾脏损伤tting-lethal（SL）大鼠中的病理作用，而肾脏损伤（SL）携带了ET_B受体基因中自然存在的脱粒。 Doca-Salt，纯合大鼠的ERTSORSTOR-627（ET_A受体拮抗剂）的慢性血压典型治疗中，与两组中的hyprophy相比，慢性病。 - 型盐诱导的高血压中的大鼠。肾脏失败（ARF）在融合后的7天进行了检查，在肾脏内皮素1含量中，纯合ARF大鼠的恢复明显延迟侵蚀蛋白在缺血性ARF的发展中不发挥重要作用，但可能参与缺血/再现引起的肾脏的恢复过程。

项目成果

西田昌広: "Role of Endothelia ET_B receptor in the pathogenesis of ischemic acute renal failure"J. Cardiovasc. Pharmacol. (印刷中). (2002)

Masahiro Nishida：“内皮细胞 ET_B 受体在缺血性急性肾衰竭发病机制中的作用”J. Cardiovasc（正在出版）。

松村靖夫: "エンドセリン受容体拮抗薬と内皮機能"血圧. 8. 67-74 (2001)

Yasuo Matsumura：“内皮素受体拮抗剂和内皮功能”血压。8. 67-74 (2001)

MATSUMURA Yasuo, KURO Toshihiko, KOBAYASHI Yutaka, KONISHI Fumiko, TAKAOKA Masanori, WESSALE Jerry L., OPGENORTH Terry j., GARIEPY Cheryl E. and YANAGISAWA Masashi: "Increased susceptivity to deoxycorticosterone acetate-salt-induce hypertension in endothe

MATSUMURA​​ Yasuo、KURO Toshihiko、KOBAYASHI Yutaka、KONISHI Fumiko、TAKAOKA Masanori、WESSALE Jerry L.、OPGENORTH Terry j.、GARIEPY Cheryl E. 和 YANAGISAWA Masashi：“内皮细胞对醋酸脱氧皮质酮盐的敏感性增加可诱发高血压

松村靖夫: "Exaggerated vascular and renal pathology in deoxycorticosterone acetate-salt, endothelin-B receptor-deficient rats"Circulation. 102. 2765-2773 (2000)

Yasuo Matsumura：“醋酸脱氧皮质酮盐、内皮素 B 受体缺陷大鼠的血管和肾脏病理学夸大”循环。 102. 2765-2773 (2000)

松村靖夫: "Enhanced blood pressure sensitivity to DOCA-salt treatment in endothelin ET_B receptor-deficient rats"Br. J. Pharmacol. 129. 1060-1062 (2000)

Yasuo Matsumura：“内皮素 ET_B 受体缺陷大鼠对 DOCA 盐治疗的血压敏感性增强”Br. J. Pharmacol. 129. 1060-1062 (2000)