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

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 μM)–pre-contracted mesenteric rings, CMMTT (10−14 –10− 6 M) induced a concentration-dependent relaxation [pD2 = 10.26 ± 0.05, Emax = 80.8 ± 5.8%], and this effect was almost abolished after either removal of the vascular endothelium [Emax = 17.7 ± 4.2%, P<0.001], removal of the vascular endothelium plus100 μM Nω-nitro-L-arginine methyl esther (L-NAME) [Emax = 21.0 ± 2.0 %, P<0.001], or after pre-treatment of the rings with 100 μM L-NAME [Emax = 13.3 ± 2.4%, P<0.001] or 10 μM 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) [Emax = 13.6 ± 4.8%, P<0.001]. However, endothelium-dependent relaxation induced by CMMTT was not significantly modified after 1 μM indomethacin plus 1 nM atropine [pD2 = 11.12 ± 0.08, Emax = 73.8 ± 5.15%] or 100 nM charybdotoxin (ChTX) plus 100 nM apamin [pD2 = 10.89 ± 0.08, Emax = 58.91 ± 9.8%]. In mesenteric rings, CMMTT (10−6M) 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. Keywords:: mesoionic compound, superior mesenteric artery, nitric oxide (NO), NO–cGMP pathway, vasodilation