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- Title
Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation.
- Authors
Park, Sang; Noh, Hyun; Sung, Dong; Kim, Jae; Kim, Jeong; Ryu, Shin-Young; Kang, KyeongJin; Kim, Bokyung; Bae, Young; Cho, Hana
- Abstract
Hydrogen peroxide (HO) is an endothelium-derived hyperpolarizing factor. Since opposing vasoactive effects have been reported for HO depending on the vascular bed and experimental conditions, this study was performed to assess whether HO acts as a vasodilator in the rat mesenteric artery and, if so, to determine the underlying mechanisms. HO elicited concentration-dependent relaxation in mesenteric arteries precontracted with norepinephrine. The vasodilatory effect of HO was reversed by treatment with dithiothreitol. HO-elicited vasodilation was significantly reduced by blocking 4-aminopyridine (4-AP)-sensitive Kv channels, but it was resistant to blockers of big-conductance Ca-activated K channels and inward rectifier K channels. A patch-clamp study in mesenteric arterial smooth muscle cells (MASMCs) showed that HO increased Kv currents in a concentration-dependent manner. HO speeded up Kv channel activation and shifted steady state activation to hyperpolarizing potentials. Similar channel activation was seen with oxidized glutathione (GSSG). The HO-mediated channel activation was prevented by glutathione reductase. Consistent with S-glutathionylation, streptavidin pull-down assays with biotinylated glutathione ethyl ester showed incorporation of glutathione (GSH) in the Kv channel proteins in the presence of HO. Interestingly, conditions of increased oxidative stress within MASMCs impaired the capacity of HO to stimulate Kv channels. Not only was the HO stimulatory effect much weaker, but the inhibitory effect of HO was unmasked. These data suggest that HO activates 4-AP-sensitive Kv channels, possibly through S-glutathionylation, which elicits smooth muscle relaxation in rat mesenteric arteries. Furthermore, our results support the idea that the basal redox status of MASMCs determines the response of Kv currents to HO.
- Subjects
HYDROGEN peroxide; AMINOPYRIDINES; ENDOTHELIUM-derived hyperpolarizing factor; VASODILATION; NORADRENALINE; POTASSIUM channels; GLUTATHIONE; MESENTERIC artery
- Publication
Pflügers Archiv: European Journal of Physiology, 2015, Vol 467, Issue 2, p285
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-014-1513-3