通过抑制大鼠爪中的血管紧张素转换酶和氨肽酶P增强缓激肽的促炎作用

Potentiation of the pro-inflammatory effects of bradykinin by inhibition of angiotensin-converting enzyme and aminopeptidase P in rat paws.

作者信息

Damas J, Liégeois J F, Simmons W H

机构信息

Départment de Physiologie humaine, Université de Liége, Belgium.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1996 Nov;354(5):670-6. doi: 10.1007/BF00170844.

DOI:10.1007/BF00170844

PMID:8938668

Abstract

The influence of some peptidase inhibitors on oedema and plasma extravasation induced by bradykinin and carrageenan in rat paw was evaluate. Bradykinin-induced oedema in normal rats was increased by o-phenanthroline (3.10(-2) M), by captopril (10(-6) M to 10(-4) M), by lisinopril (10(-6) M to 10(-4), or by lisinopril (10(-5) M) in combination with apstatin (8.10(-5) M or 1.4 10(-4) M). It was not modified by phosphoramidon (10(-6) M to 10(-5) M) and by diprotin A (10(-3) M). It was increased by mergepta at high concentrations (2.10(-4) M). Mergepta did not increase the potentiating effect of captopril. Carrageenan-oedema in normal rats was increased by captopril (10(-5) M), lisinopril (10(-5) M) and apstatin (1.4 10(-4) M. It was not modified by mergepta (10(-4) M), phosphoramidon (10 (-5) M) and diprotin A (109-3) M). Des-Arg1-bradykinin and Des-Arg9-bradykinin have low oedema-promoting effects. Captopril (10(-5) M) increased the effects of bradykinin but not those of carrageenan in kininogen-deficit Brown Norway rats. Angiotensin-converting enzyme and aminopeptidase P appear to be main kinin-inactivating enzymes in rat paws. Carboxypeptidase N, neutral endopeptidase 24.11 and dipeptidyl(amino)peptidase IV do not play a significant role in this inactivation.

摘要

评估了一些肽酶抑制剂对缓激肽和角叉菜胶诱导的大鼠爪部水肿及血浆外渗的影响。邻菲罗啉（3.10⁻² M）、卡托普利（10⁻⁶ M至10⁻⁴ M）、赖诺普利（10⁻⁶ M至10⁻⁴ M）或赖诺普利（10⁻⁵ M）与阿普他汀（8.10⁻⁵ M或1.4×10⁻⁴ M）联合使用可增加正常大鼠中缓激肽诱导的水肿。磷酰胺（10⁻⁶ M至10⁻⁵ M）和二丙嗪A（10⁻³ M）对其无影响。高浓度（2.10⁻⁴ M）的美替帕肽可增加水肿。美替帕肽不会增强卡托普利的增效作用。卡托普利（10⁻⁵ M）、赖诺普利（10⁻⁵ M）和阿普他汀（1.4×10⁻⁴ M）可增加正常大鼠中角叉菜胶诱导的水肿。美替帕肽（10⁻⁴ M）、磷酰胺（10⁻⁵ M）和二丙嗪A（10⁻³ M）对其无影响。去精氨酸1-缓激肽和去精氨酸9-缓激肽的促水肿作用较弱。卡托普利（10⁻⁵ M）可增强激肽原缺乏的棕色挪威大鼠中缓激肽的作用，但不增强角叉菜胶的作用。血管紧张素转换酶和氨肽酶P似乎是大鼠爪部主要的激肽失活酶。羧肽酶N、中性内肽酶24.11和二肽基（氨基）肽酶IV在这种失活过程中不起重要作用。