PT  - JOURNAL ARTICLE
AU  - Adebayo O. Oyekan
TI  - Differential Effects of 20-Hydroxyeicosatetraenoic Acid on Intrarenal Blood Flow in the Rat
AID  - 10.1124/jpet.104.080218
DP  - 2005 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1289--1295
VI  - 313
IP  - 3
4099  - http://jpet.aspetjournals.org/content/313/3/1289.short
4100  - http://jpet.aspetjournals.org/content/313/3/1289.full
SO  - J Pharmacol Exp Ther2005 Jun 01; 313
AB  - We recently demonstrated that endothelin-1-induced medullary vasodilation despite a potent cortical vasoconstriction in the rat kidney may be accounted for by 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study characterized the effects of 20-HETE and its metabolites, 20-hydroxy prostaglandin E2 (20-OH PGE2) and 20-hydroxy prostaglandin F2α (20-OH PGF2α), and the contribution of nitric oxide (NO) and prostanoids to the changes evoked in cortical blood flow (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 PGF2α or 20-OH PGE2, accounting for the vasoconstriction or vasodilation, respectively, in the cortex and medulla. Renal intra-arterial infusion of 1, 2.5, 5, and 10 ng/min 20-HETE decreased CBF 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 PGF2α mimics the effects of 20-HETE, as did PGF2α. 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 PGF2α. However, SQ29548 ([1S-[1α,2α(Z),3α,4α]]-7-[3[[2-[(phenylamino)carbonyl[hydrazino]methyl]-7-oxabicyclo]2.2.1]hept-2-yl]-5-heptenoic acid) (0.1 mg/kg), a prostaglandin H2/thromboxane A2 receptor antagonist, blunted the cortical and medullary hemodynamic effects elicited by 20-HETE, 20-OH PGE2, 20-OH PGF2α, and PGF2α but not PGE2. Nω-l-nitro arginine methyl ester (5 mg/kg), the inhibitor of NO synthase, exacerbated the cortical constrictor effects of 20-HETE and 20-OH PGF2α 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. The American Society for Pharmacology and Experimental Therapeutics