Akademik Veri Yönetim Sistemi
BIOLOGICAL & PHARMACEUTICAL BULLETIN, cilt.44, sa.9, ss.1220-1229, 2021 (SCI-Expanded)
The vascular action of trimethylamine-N-oxide (TMAO)-the gut microbiota-derived metabolite-in contributing cardiovascular disease is a controversial topic. A recent study has shown that acute exposure of TMAO at moderate concentrations inhibits endothelium-dependent hyperpolarization (EDH)-type relaxations selectively in rat isolated femoral arteries, but not in mesenteric arteries. Here we determined the efficacy of higher TMAO concentrations with longer exposure times on vascular reactivity in rat isolated superior mesenteric arteries. Acetylcholine-induced EDH-type relaxations were examined before and after incubation with TMAO (0.1-10mM) at increasing exposure times (1-24h). One- and 4-h-incubations with TMAO at 0.1-3mM did not cause any change in EDH-type relaxations. However, when the incubation time was increased to 24h, responses to acetylcholine were reduced in arteries incubated with I-3mM TMAO. In addition, at higher TMAO concentration (10mM) the decrease in EDH relaxations could be detected both in 4-h- and 24-h-incubations. The EDH-relaxations were preserved in rings incubated with 10mM TMAO for 24h in the presence of SKA-31 (10 mu M), the small (SKCa)- and intermediate (IKCa)-conductance calcium-activated potassium channel activator. Contractile responses to phenylephrine increased in arteries exposed to 10mM TMAO for 24h. Interestingly, nitric oxide (NO)-mediated relaxations remained unchanged in arteries treated for 24h at any TMAO concentration. Our study revealed that TMAO selectively disrupted EDH-type relaxations time-dependently without interfering with NO-induced vasodilation in rat isolated mesenteric arteries. Disruption of these relaxations may help explain the causal role of elevated TMAO levels in certain vascular diseases.