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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on March 15, 2005; DOI: 10.1124/jpet.104.080218

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Received for publication November 5, 2004.
Revised March 14, 2005.
Accepted for publication March 14, 2005.

Differential effects of 20-hydroxy eicosatetraenoic acid (20-HETE) on intrarenal blood flow in the rat

Adebayo O Oyekan 1*

1 Center for Cardiovascular Diseases, Texas Southern University

* Address correspondence to: E-mail: oyekan_ao{at}tsu.edu

Abstract

We recently demonstrated that endothelin (ET)-1-induced medullary vasodilation despite a potent cortical vasoconstriction in the rat kidney may be accounted for by 20-HETE production. This study characterized the effects of 20-HETE and its metabolites -20-OH PGE2 and 20-OH PGF2{alpha}, and the contribution of nitric oxide (NO) and prostanoids to the changes evoked in cortical (CBF) and medullary blood flow (MBF). We tested the hypothesis that 20-HETE produces qualitatively different regional hemodynamic effects in the kidney with 20-OH PGF2{alpha}or 20-OH PGE2 accounting for the vasoconstriction or vasodilation, respectively, in the cortex and medulla. Renal intraarterial infusion of 20-HETE 1,2.5, 5, and 10 ng/min decreased CBF (above basal values) by 10±3, 24±4, 40±7, and 58±9 perfusion units (PU), respectively, but increased MBF by 4±2, 16±4, 27±3, and 41±10 PU, respectively. 20-OH PGF2{alpha}mimics the effects of 20-HETE as did PGF2{alpha}. However, 20-OH PGE2 increased both CBF and MBF as did PGE2. Indomethacin (5 mg/kg) blunted the effects of 20-HETE but not that of 20-OH PGE2 and 20-OH PGF2{alpha}. However, SQ29548 ([1S-[1{alpha},2{alpha}(Z), 3{alpha},4{alpha}]]-7-[3[[2-[(phenylamino)carbonyl[hydrazino] methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid) (0.1 mg/kg), a PGH2/TxA2 (TP) receptor antagonist, blunted the effects on the cortex and medulla elicited by 20-HETE, 20-OH PGE2,20-OH PGF2{alpha}and PGF2{alpha}but not PGE. L-NAME (5 mg/kg), the inhibitor of NO synthase, exacerbated the cortical constrictor effects of 20-HETE and 20-OH PGF2{alpha} without affecting the medullary perfusion produced by 20-HETE or its metabolites. These findings suggest that 20-HETE through its hydroxyl metabolites produced differential effects in the kidney. The medullary perfusion appears to be independent of NO.


Key words: 20-HETE, 20-OH PGE2, 20-OH PGF2alpha, cortical blood flow, medullary blood flow, nitric oxide


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