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Regulation of preglomerular microvascular 20-hydroxyeicosatetraenoic acid levelsby salt depletion.

Mairead A Carroll, Rowena Kemp, Monica K Cheng, John C McGiff

Med Sci Monit 2001; 7(4): BR567-572

ID: 421102


BACKGROUND: 20-hydroxyeicosatetraenoic acid (20-HETE) is the preeminentrenal eicosanoid. The protean properties of 20-HETE - vasoactivity, mitogenicity and modulation of transportin key nephron segments - serve as the basis for the essential roles of 20-HETE in the regulation ofthe renal circulation and electrolyte excretion and as a second messenger for endothelin-1 (ET-1) anda mediator of selective renal effects of angiotensin II (AII). Renal autoregulation and tubular glomerularfeedback are mediated by 20-HETE through constriction of preglomerular microvessels, particularly afferentarterioles. METHODS AND RESULTS: We had reported that rat preglomerular microvessels (PGMV; afferent-interlobular-arcuate/interlobular)in response to angiotensin II (AII) generate primarily 20-HETE and lesser quantities of 19-HETE. We havenow addressed a possible link between the renin-angiotensin-system (RAS) and induction of cyclooxygenase(COX-2). As Na+ deprivation induces COX-2 expression/activity in the renal cortex and AII stimulatesrelease of 20-HETE from PGMV, we used a stimulus, low dietary salt, to activate the RAS and COX-2 andthereby explore potential interactions involving 20-HETE and COX-2. CONCLUSIONS: The capacity of COXto metabolize 20-HETE to prostaglandin analogs e.g., 20-OH PGF2a and 20-OH PGE2, may be critical to modifyingthe renal vascular and tubular actions of the eicosanoids.

Keywords: Animals, Arachidonic Acid, Capillaries, Chromatography, High Pressure Liquid, Cytochrome P-450 Enzyme System, Hydroxyeicosatetraenoic Acids, Isoenzymes, Kidney Glomerulus, Male, Prostaglandin-Endoperoxide Synthase, Rats, Rats, Sprague-Dawley, Research Support, U.S. Gov, Sodium Chloride, Spectrum Analysis, Mass, Venules