title: Involvement of guanylate cyclase and K+ channels in relaxation evoked by ferulate nitrate in rat aorta artery.
abstract: Vasorelaxant properties of N-2-(ferulamidoethyl)-nitrate (ferulate nitrate, FLNT), a newly synthesized nitrate, were compared with those of isosorbide dinitrate, nicorandil, nitroglycerin, and 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) in rat aorta pre-contracted by phenylephrine. FLNT produced vasorelaxation in a concentration-dependent manner (0.1 - 100 µM). The degree of relaxation induced by FLNT was similar to that induced by isosorbide dinitrate. In addition, removal of endothelium did not affect the relaxant effect of FLNT. FLNT caused a rightward shift of the cumulative concentration-response curves of phenylephrine and reduced the maximal efficacy of contraction. 1H-[1,2,4]Oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 µM) and K(+)-channel blockers charybdotoxin (CHT, 0.1 µM) and BaCl(2) (1 µM) reduced the relaxant effect of FLNT in the endothelium-denuded arteries, whereas glibenclamide (1 µM) and 4-aminopyridine (1 mM) failed to influence FLNT-induced vasorelaxation. Furthermore, in the presence of ODQ, both CHT (0.1 µM) and BaCl(2) (1 µM) still significantly reduced the relaxation evoked by FLNT. Pretreatment of vessels with hydroxocobalamin, a nitric oxide scavenger, abolished the FLNT effect. These findings demonstrate that FLNT induces relaxation of the rat aorta rings endothelium-independently. Furthermore, we demonstrated that FLNT-induced vasorelaxation is related to its stimulation of soluble guanylate cyclase and activation of K(+) channels.
authors.affiliation: Department of Pharmacology, General Hospital of Beijing Military Command, Beijing, China. wangzhanqing2049@yahoo.com.cn
authors.forename: Zhan-Qing
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Jing-Feng
authors.initials: JF
authors.lastname: Xu
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Wang
authors.forename: Wei-Juan
authors.initials: WJ
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006162:Guanylate Cyclase / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D003373:Coumaric Acids; D015221:Potassium Channels; C004999:ferulic acid; D006162:Guanylate Cyclase