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Am J Physiol Regul Integr Comp Physiol 277: R607-R623, 1999;
0363-6119/99 $5.00
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Vol. 277, Issue 3, R607-R623, September 1999

INVITED REVIEW
20-HETE and the kidney: resolution of old problems and new beginnings

John C. McGiff1 and John Quilley2

1 Department of Pharmacology, New York Medical College, Valhalla, New York 10595; and 2 Department of Cell Biology, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084

The protean properties of 20-hydroxyeicosatetraenoic acid (HETE), vasoactivity, mitogenicity, and modulation of transport in key nephron segments, serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and electrolyte excretion and as a second messenger for endothelin-1 and mediator of selective renal effects of ANG II. Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular arterioles, responses that are maintained by 20-HETE inhibition of calcium-activated potassium channels. 20-HETE modulates ion transport in the proximal tubules and the thick ascending limb by affecting the activities of Na+-K+-ATPase and the Na+-K+-2Cl- cotransporter, respectively. The range and diversity of activity of 20-HETE derives in large measure from COX-dependent transformation of 20-HETE to products affecting vasomotion and salt and water excretion. Nitric oxide (NO) exerts a negative modulatory effect on 20-HETE formation; inhibition of NO synthesis produces marked perturbation of renal function resulting from increased 20-HETE production. 20-HETE is an essential component of interactions involving several hormonal systems that have central roles in blood pressure homeostasis, including angiotensins, endothelins, NO, and cytokines. 20-HETE is the preeminent renal eicosanoid, overshadowing PGE2 and PGI2. This review is intended to provide evidence for the physiological roles for cytochrome P-450-derived eicosanoids, particularly 20-HETE, and seeks to extend this knowledge to a conceptual framework for overall cardiovascular function.

20-hydroxyeicosatetraenoic acid; cyclooxygenase; cytochrome P-450 monooxygenases; endothelin; nitric oxide; potassium channels; preglomerular microvessels; renal autoregulation; thick ascending limb; tubuloglomerular feedback; tumor necrosis factor


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