title: Vasorelaxation induced by a new naphthoquinone-oxime is mediated by NO-sGC-cGMP pathway.
abstract: It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4-(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10, 15, 20 and 30 mg/Kg, i.v.) produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10(-8) M to 10(-4) M). In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO) pathway. Additionally, Oxime S1 (30 and 100 µM) significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively) measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM) prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting a role for potassium channels, more precisely Kir, Kv and KATP channels. We observed the involvement of BKCa channels in Oxime S1-induced relaxation in mesenteric artery rings. In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC) and K+ channels.
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. brunapvd@gmail.com.
authors.forename: Bruna P V
authors.initials: BP
authors.lastname: Dantas
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. thaispribeiro@hotmail.com.
authors.forename: Thaís P
authors.initials: TP
authors.lastname: Ribeiro
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. val_farm@hotmail.com.
authors.forename: Valéria L
authors.initials: VL
authors.lastname: Assis
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. fabiola.fialho@gmail.com.
authors.forename: Fabíola F
authors.initials: FF
authors.lastname: Furtado
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. kivia_sales@hotmail.com.
authors.forename: Kívia S
authors.initials: KS
authors.lastname: Assis
authors.affiliation: Molecular Sciences Department, Federal Rural University of Pernambuco, Recife, PE 52171-900, Brazil. quimicajeizi@yahoo.com.br.
authors.forename: Jeziane S
authors.initials: JS
authors.lastname: Alves
authors.affiliation: Molecular Sciences Department, Federal Rural University of Pernambuco, Recife, PE 52171-900, Brazil. taniasarmento@dcm.ufrpe.br.
authors.forename: Tania M S
authors.initials: TM
authors.lastname: Silva
authors.affiliation: Molecular Sciences Department, Federal Rural University of Pernambuco, Recife, PE 52171-900, Brazil. ccelso@dcm.ufrpe.br.
authors.forename: Celso A
authors.initials: CA
authors.lastname: Camara
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil.
authors.forename: Maria S
authors.initials: MS
authors.lastname: França-Silva
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. robveras@msn.com.
authors.forename: Robson C
authors.initials: RC
authors.lastname: Veras
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. isacmed@uol.com.br.
authors.forename: Isac A
authors.initials: IA
authors.lastname: Medeiros
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. jacicarlos@ccm.ufpb.br.
authors.forename: Jacicarlos L
authors.initials: JL
authors.lastname: Alencar
authors.affiliation: Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil. valdir@cbiotec.ufpb.br.
authors.forename: Valdir A
authors.initials: VA
authors.lastname: Braga
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000071756:Soluble Guanylyl Cyclase; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009285:Naphthoquinones; D020030:Nitric Oxide Donors; D010091:Oximes; D015221:Potassium Channels; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; C483060:naphthoquinone monooxime; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP