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新型血管紧张素转换酶抑制剂CGS 16617的肾脏作用

Renal actions of the new angiotensin converting enzyme inhibitor CGS 16617.

作者信息

Levens N R

机构信息

Research Department, Ciba-Geigy Corporation, Summit, NJ 07901.

出版信息

Arch Int Pharmacodyn Ther. 1988 Mar-Apr;292:266-80.

PMID:2840040
Abstract

Renal actions of the new angiotensin converting enzyme inhibitor CGS 16617 were evaluated in anesthetized dogs. Intravenous administration of 0.4 mg/kg CGS 16617 resulted in complete inhibition of the pressor response to 1 microgram angiotensin I (ANG I) for a 2 hr period. Over this period, i.v. injection of CGS 16617 significantly reduced mean arterial pressure (MAP) by 9 mmHg and significantly increased renal blood flow and glomerular filtration rate. Sodium and water excretion increased significantly following converting enzyme inhibition. Intravenous injection of CGS 16617 also markedly decreased urine osmolality and produced a highly significant increase in free water formation. Intravenous infusion of 0.5 microgram/kg per min saralasin also completely inhibited the pressor response produced by 1 microgram of ANG I. Except for the absence of a significant change in urinary osmolality, the changes in MAP and renal function produced by saralasin were essentially identical to those produced by CGS 16617. The results presented in this study demonstrate that the new converting enzyme inhibitor CGS 16617 has potent actions on renal function. The similarity of the changes in blood pressure and renal function produced by CGS 16617 to those of saralasin may suggest that the consequences of angiotensin converting enzyme inhibition in this model can largely be explained by inhibition of the renin-angiotensin system.

摘要

在麻醉犬身上评估了新型血管紧张素转换酶抑制剂CGS 16617的肾脏作用。静脉注射0.4mg/kg CGS 16617可在2小时内完全抑制对1微克血管紧张素I(ANG I)的升压反应。在此期间,静脉注射CGS 16617使平均动脉压(MAP)显著降低9mmHg,并显著增加肾血流量和肾小球滤过率。血管紧张素转换酶抑制后钠和水排泄显著增加。静脉注射CGS 16617还显著降低尿渗透压,并使自由水生成显著增加。静脉输注0.5微克/千克每分钟的沙拉新也完全抑制了1微克ANG I产生的升压反应。除尿渗透压无显著变化外,沙拉新引起的MAP和肾功能变化与CGS 16617引起的基本相同。本研究结果表明,新型血管紧张素转换酶抑制剂CGS 16617对肾功能有强大作用。CGS 16617引起的血压和肾功能变化与沙拉新的相似,这可能表明在该模型中血管紧张素转换酶抑制的后果很大程度上可由肾素-血管紧张素系统的抑制来解释。

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