Trimethylamine-N-oxide Specifically Impairs Endothelium-Derived Hyperpolarizing Factor-Type Relaxation in Rat Femoral Artery
| Autor: | Mihoka Kojima, Tsuneo Kobayashi, Kumiko Taguchi, Takayuki Matsumoto, Keisuke Takayanagi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endothelium-derived hyperpolarizing factor Pharmaceutical Science Femoral artery Apamin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine.artery medicine Superior mesenteric artery Mesenteric arteries Pharmacology biology Endothelium-derived relaxing factor General Medicine Potassium channel Nitric oxide synthase 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry 030220 oncology & carcinogenesis biology.protein |
| Zdroj: | Biological and Pharmaceutical Bulletin. 43:569-573 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b19-00957 |
| Popis: | 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 EDHF, ACh-induced relaxation was low, and there were no differences between the control and TMAO-treated groups with respect to both arteries. In femoral arteries, TMAO slightly reduces ACh-induced relaxation in the presence of indomethacin (preserved NO and EDHF signals) but does not affect ACh-induced NO-mediated relaxation under the combined presence of indomethacin, TRAM-34, and apamin. These results suggest that acute treatment with TMAO specifically impairs EDHF-mediated relaxation in the femoral arteries but not in the superior mesenteric arteries. These novel observations show that TMAO is a causative factor in the development of peripheral arterial disease. |
| Databáze: | OpenAIRE |
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