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 [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 N ω -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 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 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.

Effect of Gamma- Irradiation on Structure, Morphology and Thermal Properties of Novel Polyamide Based Thermoset Obtained by Double Cycloaddition

“…The versatile structural characteristics and properties of mesoionic compounds have gained the attention of many researchers to the field of photonics and non-linear optical studies [21][22][23][24] and medicinal chemistry [25][26][27][28][29][30][31]. Admitting the fact that meso-ionic compounds are well explored in the field of non-linear optical studies and medicinal chemistry, these are less explored in the field of polymer synthesis.…”

Drug Resistance Modulation in Staphylococcus Aureus, a New Biological Activity for Mesoionic Hydrochloride Compounds

“…Due to their inherent structural characteristics, mesoionic compounds have aroused research interest in photonics, nonlinear optical studies [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ] and medicinal chemistry, where a wide range of biological activities have been discovered, as summarized in several review articles [ 9 , 10 , 11 ]. They can be biologically active, for example, mesoionic 2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-1,3-thiazolium-5-thiolate induces vasorelaxation [ 12 ].…”

Synthesis and preliminary ex vivo evaluation of the spasmolytic activity of 1,3-thiazolium- and 1,3,4-thiadiazolium-5-methylthio- and 5-thioacetate derivatives

“…In the latter area, the literature describes a wide range of biological activities associated with this class of compounds, including, among others, analgesic, anti-inflammatory, anticancer, antimicrobial, antihypertensive, antiplatelet, thrombolytic, trypanocidal and leishmanicidal activities (7)(8)(9)(10)(11)(12)(13).…”