Trimethylamine-N-oxide Specifically Impairs Endothelium-Derived Hyperpolarizing Factor-Type Relaxation in Rat Femoral Artery.

Trimethylamine-N-oxide Specifically Impairs Endothelium-Derived Hyperpolarizing Factor-Type Relaxation in Rat Femoral Artery. Biol Pharm Bull. 2020;43(3):569-573 Authors: Matsumoto T, Kojima M, Takayanagi K, Taguchi K, Kobayashi T Abstract Although substantial evidence suggests that an increase in the level of trimethylamine-N-oxide (TMAO) is associated with the risk of cardiovascular diseases, including atherosclerosis, chronic kidney diseases, and hypertension, the direct effect of TMAO on vascular endothelial function remains unclear. Therefore, we investigated the acute effects of TMAO on endothelium-dependent relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries and femoral arteries of rat. In endothelium-intact preparations, it was observed that TMAO (300 µmol/L for 60 min) did not affect ACh-induced relaxation in either of the two arteries. In endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation under nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibitions by Nω-nitro-L-arginine (L-NNA) and indomethacin, respectively, TMAO specifically impairs the relaxation in femoral arteries but not in the superior mesenteric arteries. Under the inhibitory actions of NOS and as well as blockade of intermediate-conductance calcium-activated potassium channel (IKCa) (by TRAM-34) and small-conductance calcium-activated potassium channel (SKCa) (by apamin), which are putative sources of ED...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research