title: Endothelium-derived nitric oxide contributes to the vasorelaxant response induced by mesoionic 2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-1;3-thiazolium-5-thyolate (CMMTT) in rats.
abstract: This study was performed to investigate the mechanisms involved in the vasorelaxation induced by mesoionic 2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-1;3-thiazolium-5-thyolate (CMMTT), a newly synthesized mesoionic compound, in rat superior mesenteric arteries. In phenylephrine (10 microM)-pre-contracted mesenteric rings, CMMTT (10(-14) - 10(-6) M) induced a concentration-dependent relaxation [pD(2) = 10.26 +/- 0.05, E(max) = 80.8 +/- 5.8%], and this effect was almost abolished after either removal of the vascular endothelium [E(max) = 17.7 +/- 4.2%, P<0.001], removal of the vascular endothelium plus100 microM N(omega)-nitro-L-arginine methyl esther (L-NAME) [E(max) = 21.0 +/- 2.0 %, P<0.001], or after pre-treatment of the rings with 100 microM L-NAME [E(max) = 13.3 +/- 2.4%, P<0.001] or 10 microM 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) [E(max) = 13.6 +/- 4.8%, P<0.001]. However, endothelium-dependent relaxation induced by CMMTT was not significantly modified after 1 microM indomethacin plus 1 nM atropine [pD(2) = 11.12 +/- 0.08, E(max) = 73.8 +/- 5.15%] or 100 nM charybdotoxin (ChTX) plus 100 nM apamin [pD(2) = 10.89 +/- 0.08, E(max) = 58.91 +/- 9.8%]. In mesenteric rings, CMMTT (10(-6) M) was able to increase nitric oxide (NO)(x) levels, and this effect was abolished after removal of the vascular endothelium. In conclusion, the present study, using combined functional and biochemical approaches, demonstrated that CMMTT induced a significant vasorelaxant effect, almost completely mediated by the endothelium, likely via NO release and activation of the NO-cGMP pathway.
authors.affiliation: Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Brazil.
authors.forename: Karla Veruska Marques
authors.initials: KV
authors.lastname: Cavalcante
authors.forename: Nádja de Azevedo
authors.initials: Nde A
authors.lastname: Correia
authors.forename: Katy Lísias Gondim
authors.initials: KL
authors.lastname: Dias
authors.forename: Darizy Flávia
authors.initials: DF
authors.lastname: Silva
authors.forename: José Couras
authors.initials: JC
authors.lastname: Silva-Filho
authors.forename: Islania Giselia Albuquerque
authors.initials: IG
authors.lastname: Araújo
authors.forename: Bruno Farias
authors.initials: BF
authors.lastname: Lira
authors.forename: Petrônio
authors.initials: P
authors.lastname: Athayde-Filho
authors.forename: Isac Almeida
authors.initials: IA
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C541648:2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-1;3-thiazolium-5-thyolate; D001685:Biological Factors; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D013844:Thiazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D010656:Phenylephrine; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester