20-HETE and the kidney: resolution of old problems and new beginnings.
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.
McGiff
J C
JC
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA. John_McGiff@nymc.edu
Quilley
J
J
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D017136:Ion Transport; D007668:Kidney / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D012079:Renal Circulation / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
D002352:Carrier Proteins; D006893:Hydroxyeicosatetraenoic Acids; D028021:Sodium-Potassium-Chloride Symporters; D009569:Nitric Oxide; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D000254:Sodium-Potassium-Exchanging ATPase