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Articles in PresS, published online ahead of print November 5, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00239.2002
Submitted on July 1, 2002
Accepted on October 21, 2002
1 Department of Pharmacology, New York Medical College, Valhalla, NY, USA
* To whom correspondence should be addressed. E-mail: mairead_carroll{at}nymc.edu.
20-hydroxyeicosatetraenoic acid (HETE), a potent vasoconstrictor, is generated by the cytochrome P450 (CYP)
-hydroxylases, and is the principal eicosanoid produced by preglomerular microvessels (PGA). It is released from PGA by angiotensin II and is subject to metabolism by cyclooxygenase (COX). As 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/interlobular arteries) obtained from 6 to 7 week old male Sprague-Dawley rats fed either normal salt (NS; 0.4% NaCl) or LS (0.05% NaCl) diets for 10 days. With NS intake, the levels of 20-HETE recovered was similar in arcuate/interlobular arteries and interlobar arteries: 30.1±8.5 vs. 24.6±5.3 ng/mg protein/30 min, respectively. A LS diet increased 20-HETE levels in the incubate of either arcuate/interlobular or interlobar renal arteries only when COX was inhibited. Addition of indomethacin (10µM) to the incubate of arteries obtained from LS diet fed rats resulted in a two- to three-fold increase in 20-HETE release from arcuate/interlobular arteries, from 39.1±13.2 to 101.8±42.6 ng/mg protein/30 min (p<0.03), and interlobar arteries, from 31.7±15.1 to 61.9±29.4 ng/mg protein/30 min (p<0.05), compared to release of 20-HETE when COX was not inhibited. A LS diet enhanced vascular expression of CYP4A and COX-2 in arcuate/interlobular arteries, COX-1 being unaffected. Metabolism of 20-HETE by COX is proposed to represent an important regulatory mechanism in setting preglomerular microvascular tone.
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