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CARDIOVASCULAR

Differential Effects of 20-Hydroxyeicosatetraenoic Acid on Intrarenal Blood Flow in the Rat

Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas

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 F₂ (20-OH PGF₂), 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 PGF₂ 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 PGF₂ mimics the effects of 20-HETE, as did PGF₂. 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. However, SQ29548 ([1S-[1,2(Z),3,4]]-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 PGF₂, and PGF₂ but not PGE₂. N-L-nitro arginine methyl ester (5 mg/kg), the inhibitor of NO synthase, exacerbated the cortical constrictor effects of 20-HETE and 20-OH PGF₂ 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.

Address correspondence to: Adebayo O. Oyekan, Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004. E-mail: oyekan_ao{at}tsu.edu

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