Abstract

We recently demonstrated that U46619 (9-11-dideoxy-11α,9a-epoxymethano-prostaglandin F_2a) 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.N^ω-l-Nitro-arginine methyl ester (5 mg/kg), the inhibitor of NO production, attenuated the increase in MBF (75 ± 8%, p < 0.05) as did indomethacin (10 mg/kg), the inhibitor of cyclooxygenase (38 ± 5%, p < 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 < 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 K_ATP channel blocker, also blunted the increase by U46619 in MBF (58 ± 7%, p < 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 K_ATP channels but not protein kinase A.