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依那普利拉介导的激肽 B(1)受体激活和大鼠离体灌流肾脏的血管舒张。

Enalaprilat-mediated activation of kinin b(1) receptors and vasodilation in the rat isolated perfused kidney.

机构信息

Department of Nephrology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico.

出版信息

Pharmacology. 2011;87(3-4):195-203. doi: 10.1159/000324513. Epub 2011 Mar 25.

Abstract

The present study evaluated whether enalaprilat (the active form of enalapril, an angiotensin-converting enzyme inhibitor) activates B(1) receptors. We observed that the levels of B(1) receptor mRNA and protein expression were upregulated in the kidneys of diabetic rats. Bradykinin (BK)-induced renal vasodilation decreased in isolated perfused kidneys of diabetic rats, but des-Arg(9)-BK-induced renal vasodilation increased. Enalaprilat also produced vasodilation in the isolated perfused kidneys of control and diabetic rats. The response to des-Arg(9)-BK or enalaprilat was blocked by Lys-(des-Arg(9), Leu(8))-BK (a B(1) receptor antagonist) and N-nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase). These results suggest that enalaprilat activates B(1) receptors and stimulates the production of nitric oxide in the kidneys of both control and diabetic rats.

摘要

本研究评估了依那普利拉(血管紧张素转换酶抑制剂依那普利的活性形式)是否激活 B(1)受体。我们观察到,糖尿病大鼠肾脏中 B(1)受体 mRNA 和蛋白表达水平上调。在糖尿病大鼠离体灌注肾脏中,缓激肽(BK)诱导的肾血管舒张减少,但去精氨酸 9-BK 诱导的肾血管舒张增加。依那普利拉也可在正常和糖尿病大鼠的离体灌注肾脏中产生血管舒张作用。用 Lys-(des-Arg(9),Leu(8))-BK(B(1)受体拮抗剂)和 N-硝基-L-精氨酸甲酯(一氧化氮合酶抑制剂)阻断了对去精氨酸 9-BK 或依那普利拉的反应。这些结果表明,依那普利拉激活 B(1)受体并刺激正常和糖尿病大鼠肾脏中一氧化氮的产生。

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