Akademik Veri Yönetim Sistemi
Fabad Journal of Pharmaceutical Sciences, cilt.49, sa.1, ss.227-232, 2024 (Scopus)
The effect of the gut microbiota metabolite trimethylamine-(TMA) in isolated vessels is unknown. Previously TMAO, the hepatic oxidation product of TMA, at 3 mM has been shown to inhibit endothelium-dependent vasorelaxations of isolated arteries only after 24-hour interaction. In this study, the effects of TMA (at 1 mM) on endothelium-dependent relaxations with acute (1 or 4 hours) and longer (24 hours) incubation periods were evaluated in superior mesenteric arteries of rats. Acute exposure to TMA of 1 hour significantly inhibited acetylcholine-stimulated endotheliumderived hyperpolarizing (EDH) type relaxations, and this inhibition gradually intensified as the incubation period was prolonged to 4 and 24 hours. The area under the curves (AUCs) of the relaxationresponse curves after 1 and 24 hours after TMA incubation were found to be significantly different from each other. In contrast, similar AUC values were obtained after 4 and 24 hours of incubation. Contractile responses to phenylephrine, and nitric oxide (NO)- mediated relaxations of acetylcholine were similar in arteries before and after pretreatment with TMA for 24 hours. These data indicate that TMA selectively inhibits EDH-type relaxations in rat isolated mesenteric arteries. Although the inhibitory effect of TMA intensifies over time, it appears to be more pronounced during acute incubation periods. The findings strengthen the evidence that TMA is a more toxic metabolite on vascular tone than TMAO.