Regulation of preglomerular microvascular 20-hydroxyeicosatetraenoic acid levels by salt depletion.
BACKGROUND
20-hydroxyeicosatetraenoic acid (20-HETE) is the preeminent renal eicosanoid. The protean properties of 20-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 (ET-1) and a mediator of selective renal effects of angiotensin II (AII). Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular microvessels, particularly afferent arterioles.


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 have now 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 stimulates release of 20-HETE from PGMV, we used a stimulus, low dietary salt, to activate the RAS and COX-2 and thereby explore potential interactions involving 20-HETE and COX-2.


CONCLUSIONS
The capacity of COX to metabolize 20-HETE to prostaglandin analogs e.g., 20-OH PGF2a and 20-OH PGE2, may be critical to modifying the renal vascular and tubular actions of the eicosanoids.
Carroll
M A
MA
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA. mailread_carroll@nymc.edu
Kemp
R
R
Cheng
M K
MK
McGiff
J C
JC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000378:metabolism*; D014699:Venules / Q000378:metabolism*
D006893:Hydroxyeicosatetraenoic Acids; D007527:Isoenzymes; D016718:Arachidonic Acid; D012965:Sodium Chloride; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases