Renal functional effects of endothelins: Dependency on cytochrome P450-derived arachidonate metabolites

被引：0

作者：

Oyekan, AO ^{[1
]}

McAward, K ^{[1
]}

McGiff, JC ^{[1
]}

机构：

[1] New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA

来源：

BIOLOGICAL RESEARCH | 1998年 / 31卷 / 03期

关键词：

cytochrome P450 arachidonate metabolites; eicosanoids; endothelin; hypertension; renal function; 20-hydroxy-eicosatetraenoic acid (20-HETE);

D O I：

暂无

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The renal tubular and hemodynamic effects of endothelin-l (ET-I) were studied in the rat in terms of the participation of cytochrome P450 monooxygenases (CYP450)-derived arachidonic acid (AA) metabolites. The availability of specific mechanism-based inhibitors of CYP450-dependent AA metabolism has greatly facilitated studies designed to link AA metabolites generated by CYP450 to renal function. Eicosanoid products synthesized by cyclooxygenase (COX) and CYP450 can account for the renal functional effects of ET-I. Inhibition of COX decreased glomerular filtration rate (GFR) and potentiated the depression of GFR elicited by ET-I. In contrast, inhibition of CY-P450-dependent AA metabolism enhanced GFR and blunted ET-I induced increase in renal vascular resistance, yet reduced the diuretic response to ET-I. Thus, CYP450-dependent AA products depress GFR and renal blood flow, while promoting sodium excretion. The effects of ET-I on renal function correspond to those of 20-HETE, the predominant renal CYP450-derived AA metabolite.

引用

页码：209 / 215

页数：7

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