Contributions of nitric oxide and prostanoids and their signaling pathways to the renal medullary vasodilator effect of U46619 (9-11-dideoxy-11 alpha,9a-epoxymethano-prostaglandin F(2a)) in the rat.
We recently demonstrated that U46619 (9-11-dideoxy-11 alpha,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 microg/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(omega)-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.
Oyekan
Adebayo O
AO
Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas 77004, USA. Oyekan_AO@TSU.EDU
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid