title: Protein kinase A increases electrical stimulation-induced neuronal nitric oxide release in rat mesenteric artery.
abstract: The aim of this study was to analyse the possible influence of cyclic AMP-protein kinase A (cAMP-PKA) activation on neuronal nitric oxide (NO) release induced by electrical field stimulation in mesenteric arteries from Wistar Kyoto (WKY) rats. Western blot experiments demonstrated the expression of neuronal NO synthase (nNOS) in mesenteric artery from WKY rats; however, electrical field stimulation alone did not induce detectable NO release. Preincubation with forskolin allowed NO release induced by electrical field stimulation, which was abolished by: the neuronal toxine tetrodotoxin, the nNOS inhibitors 7-nitroindazole or N(omega)-propil-l-arginine (NPLA), and the PKA inhibitors N-(2-(p-Bromocinnamylamino) ethyl 5-isoquinolinesulfonamide hydrochloride (H-89) or (9R,10S,12S)-2,3,9,10,11, 12-Hexahydro-10-9-methyl-1-oxo-9,12-epoxy-1H-diindolo(1,2,3-fg:3,2,1k)pyrrolo(3,4-l)(1,6) benzodiazocine-10-carboxylic acid hexyl ester (KT-5720). Preincubation with prostacyclin also allowed the NO release induced by electrical field stimulation which was significantly decreased by: the neuronal toxine tetrodotoxin, the nNOS inhibitors 7-nitroindazole or NPLA, and the PKA inhibitors H-89 or KT-5720. The NOS inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) did not modify the vasoconstrictor response induced by electrical field stimulation. However, in the presence of forskolin or prostacyclin, l-NAME increased the vasoconstrictor response to electrical field stimulation. These results indicate that forskolin and prostacyclin allow neuronal NO release induced by electrical field stimulation through a mechanism involving cAMP-PKA activation in rat mesenteric arteries.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, C/Arzobispo Morcillo, 4, Madrid 28029, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ferrer
authors.forename: Margarita
authors.initials: M
authors.lastname: Sánchez
authors.forename: Maria del Carmen
authors.initials: MC
authors.lastname: Martín
authors.forename: Iván
authors.initials: I
authors.lastname: Márquez-Rodas
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Alonso
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.forename: Gloria
authors.initials: G
authors.lastname: Balfagón
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D005576:Colforsin; D009569:Nitric Oxide; D011464:Epoprostenol; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester