Pro-inflammatory effect of quercetin by dual blockade of angiotensin converting-enzyme and neutral endopeptidase in vivo
Pro-inflammatory effect of quercetin by dual blockade of angiotensin converting-enzyme and neutral endopeptidase in vivo
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DOI：
10.1080/10284150310001595609
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发表时间：
2003-10-01
影响因子：
3.6
通讯作者：
Cuttle, G
中科院分区：
文献类型：
--
作者：
Nicolau, M;Dovichi, SS;Cuttle, G
研究了黄酮类槲皮素对 P 物质和缓激肽诱导的大鼠组织（十二指肠、心脏、胰腺、气管和膀胱）血浆外渗的影响，以及内源性肽酶的调节作用。通过渗出的伊文思蓝染料测定血浆蛋白渗出。静脉注射P物质（1、3和10 nmol/kg）以剂量依赖性方式增加心脏、胰腺、气管和膀胱中的血浆外渗。缓激肽（3 和 10 nmol/kg，静脉注射）以剂量依赖性方式增加十二指肠、胰腺、气管和膀胱中的血浆外渗。用选定剂量的槲皮素进行预处理增强了P物质诱导的心脏、胰腺和膀胱中的血浆外渗，以及缓激肽诱导的十二指肠、心脏、气管和膀胱中的血浆外渗。中性内肽酶和血管紧张素转换酶的选择性药理学抑制分别增强了P物质和缓激肽诱导的血浆外渗，此外，用受体拮抗剂治疗表明，参与槲皮素增强血浆外渗的介质是P物质和缓激肽。血浆血管紧张素转换酶活性分析表明槲皮素抑制这种酶。这些结果表明槲皮素可增强 P 物质和缓激肽诱导的血浆外渗，这可能是由于抑制这些肽的降解酶所致。
The effect of the flavonoid quercetin on substance P- and bradykinin-induced plasma extravasation in rat tissues (duodenum, heart, pancreas, trachea and urinary bladder) was studied, and its modulation by endogenous peptidases. Plasma protein extravasation was assayed by extravasated Evans blue dye. Intravenous injection of substance P (1, 3 and 10 nmol/kg) increased the plasma extravasation in a dose-dependent manner in heart, pancreas, trachea and urinary bladder. Bradykinin (3 and 10 nmol/kg, i.v.) increased plasma extravasation in a dose-dependent manner in duodenum, pancreas, trachea and urinary bladder. Pre-treatment with a selected dose of quercetin potentiated the substance P-induced plasma extravasation in heart, pancreas and urinary bladder, and also the bradykinin-induced, plasma extravasation in duodenum, heart, trachea and urinary bladder. The selective pharmacological inhibition of neutral endopeptidase and angiotensin-converting enzyme potentiated the substance P- and bradykinin-induced plasma extiavasation, respectively, furthermore, treatment with receptor antagonists showed that the mediators involved in the potentiation of plasma extravasation by quercetin are substance P and bradykinin. Analysis of plasma angiotensin-converting enzyme activity demonstrated that quercetin inhibited this enzyme. These results suggest that quercetin potentiates plasma extravasation induced by substance P and bradykinin, and that this may result from inhibition of the degradative enzymes of these peptides.