title: Differential effects of 20-hydroxyeicosatetraenoic acid on intrarenal blood flow in the rat.
abstract: 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 E(2) (20-OH PGE(2)) and 20-hydroxy prostaglandin F(2alpha) (20-OH PGF(2alpha)), 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 PGF(2alpha) or 20-OH PGE(2), 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 PGF(2alpha) mimics the effects of 20-HETE, as did PGF(2alpha). However, 20-OH PGE(2) increased both CBF and MBF, as did PGE(2). Indomethacin (5 mg/kg) blunted the effects of 20-HETE but not that of 20-OH PGE(2) and 20-OH PGF(2alpha). However, SQ29548 ([1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3[[2-[(phenylamino)carbonyl[hydrazino]methyl]-7-oxabicyclo]2.2.1]hept-2-yl]-5-heptenoic acid) (0.1 mg/kg), a prostaglandin H(2)/thromboxane A(2) receptor antagonist, blunted the cortical and medullary hemodynamic effects elicited by 20-HETE, 20-OH PGE(2), 20-OH PGF(2alpha), and PGF(2alpha) but not PGE(2). N(omega)-L-nitro arginine methyl ester (5 mg/kg), the inhibitor of NO synthase, exacerbated the cortical constrictor effects of 20-HETE and 20-OH PGF(2alpha) 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.
authors.affiliation: Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, 77004, USA. oyekan_ao@tsu.edu
authors.forename: Adebayo O
authors.initials: AO
authors.lastname: Oyekan
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002560:Cerebrovascular Circulation / Q000187:drug effects; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007679:Kidney Medulla / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D006893:Hydroxyeicosatetraenoic Acids; D009569:Nitric Oxide; C048824:20-hydroxyprostaglandin E2; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C045749:SQ 29548; D015232:Dinoprostone; D007213:Indomethacin