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 [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 μM
Nω-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 μM
L-NAME [E
max = 13.3 ± 2.4%,
P<0.001] or 10 μM 1
H-[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 μM 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.
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