Renal arterial 20-hydroxyeicosatetraenoic acid levels: regulation by cyclooxygenase.
20-HETE, a potent vasoconstrictor, is generated by cytochrome P-450 omega-hydroxylases and is the principal eicosanoid produced by preglomerular microvessels. It is released from preglomerular microvessels by ANG II and is subject to metabolism by cyclooxygenase (COX). Because low-salt (LS) intake stimulates the renin-angiotensin system and induces renal cortical COX-2 expression, we examined 20-HETE release from renal arteries (interlobar and arcuate and interlobular arteries) obtained from 6- to 7-wk-old male Sprague-Dawley rats fed either normal salt (0.4% NaCl) or LS (0.05% NaCl) diets for 10 days. With normal salt intake, the levels of 20-HETE recovered were similar in arcuate and interlobular arteries and interlobar arteries: 30.1 +/- 8.5 vs. 24.6 +/- 5.3 ng. mg protein(-1). 30 min(-1), respectively. An LS diet increased 20-HETE levels in the incubate of either arcuate and interlobular or interlobar renal arteries only when COX was inhibited. Addition of indomethacin (10 microM) to the incubate of arteries obtained from rats fed an LS diet resulted in a two- to threefold increase in 20-HETE release from arcuate and interlobular arteries, from 39.1 +/- 13.2 to 101.8 +/- 42.6 ng. mg protein(-1). 30 min(-1) (P < 0.03), and interlobar arteries, from 31.7 +/- 15.1 to 61.9 +/- 29.4 ng. mg protein(-1). 30 min(-1) (P < 0.05) compared with release of 20-HETE when COX was not inhibited. An LS diet enhanced vascular expression of cytochrome P-4504A and COX-2 in arcuate and interlobular arteries; COX-1 was unaffected. Metabolism of 20-HETE by COX is proposed to represent an important regulatory mechanism in setting preglomerular microvascular tone.
Cheng
Monica K
MK
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
McGiff
John C
JC
Carroll
Mairead A
MA
D000818:Animals; D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008565:Membrane Proteins; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007527:Isoenzymes; D008565:Membrane Proteins; D012982:Sodium, Dietary; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D007213:Indomethacin