PT - JOURNAL ARTICLE AU - Adebayo O. Oyekan TI - Contributions of Nitric Oxide and Prostanoids and Their Signaling Pathways to the Renal Medullary Vasodilator Effect of U46619 (9-11-Dideoxy-11α,9a-Epoxymethano-Prostaglandin F<sub>2a</sub>) in the Rat AID - 10.1124/jpet.102.040170 DP - 2003 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 507--512 VI - 304 IP - 2 4099 - http://jpet.aspetjournals.org/content/304/2/507.short 4100 - http://jpet.aspetjournals.org/content/304/2/507.full SO - J Pharmacol Exp Ther2003 Feb 01; 304 AB - We recently demonstrated that U46619 (9-11-dideoxy-11α,9a-epoxymethano-prostaglandin F2a) evoked a medullary vasodilation and a reduction in blood pressure despite a potent cortical vasoconstriction in the anesthetized rat. The present study tested the hypothesis that nitric oxide (NO) and prostanoids contribute to U46619-induced increase in medullary blood flow (MBF). U46619 at 1, 3, and 5 μg/kg increased MBF (above basal values) by 16 ± 3, 45 ± 10, and 58 ± 8 perfusion units, respectively, and increased NO current in the medulla by 17 ± 4, 34 ± 7, and 60 ± 12 pA, respectively.Nω-l-Nitro-arginine methyl ester (5 mg/kg), the inhibitor of NO production, attenuated the increase in MBF (75 ± 8%, p &lt; 0.05) as did indomethacin (10 mg/kg), the inhibitor of cyclooxygenase (38 ± 5%, p &lt; 0.05), suggesting the involvement of NO and dilator prostanoids. H-Arg-Lys-Arg-Ala-Arg-Lys-Glu-OH, a synthetic peptide and selective inhibitor of cGMP-dependent protein kinase, attenuated U46619-induced medullary perfusion (52 ± 6%,p &lt; 0.05), but H-89 ((N-[2-((p-bromocinnamyl)aminoethyl)]-5-isoquinolinesulfonamide hydrochloride), a cell-permeable, selective, and potent inhibitor of cAMP-dependent protein kinase A, was without effect. Glybenclamide, a KATP channel blocker, also blunted the increase by U46619 in MBF (58 ± 7%, p &lt; 0.05). These data suggest that NO and prostanoids contribute to U46619-induced medullary perfusion and that the effects of these mediators are coupled to activation of protein kinase G and KATP channels but not protein kinase A. The American Society for Pharmacology and Experimental Therapeutics