Intermittent hypoxia in rats increases myogenic tone through loss of hydrogen sulfide activation of large-conductance Ca(2+)-activated potassium channels.
Intermittent hypoxia in rats increases myogenic tone through loss of hydrogen sulfide activation of large-conductance Ca(2+)-activated potassium channels.
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DOI：
10.1161/circresaha.110.228999
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发表时间：
2011-06-10
影响因子：
20.1
通讯作者：
Kanagy NL
中科院分区：
文献类型：
--
作者：
Jackson-Weaver O;Paredes DA;Gonzalez Bosc LV;Walker BR;Kanagy NL
Myogenic tone, an important regulator of vascular resistance, is dependent on vascular smooth muscle (VSM) depolarization, can be modulated by endothelial factors, and is increased in several models of hypertension. Intermittent hypoxia (IH) elevates blood pressure and causes endothelial dysfunction. Hydrogen sulfide (H2S), a recently described endothelium-derived vasodilator, is produced by the enzyme cystathionine γ-lyase (CSE) and acts by hyperpolarizing VSM. Determine whether IH decreases endothelial H2S production to increase myogenic tone in small mesenteric arteries. Myogenic tone was greater in mesenteric arteries from IH than Shamfrom sham rat arteries, and VSM membrane potential was depolarized in IH in comparison with Shamsham arteries. Endothelium inactivation or scavenging of H2S enhanced myogenic tone in Shamsham arteries to the level of IH. Inhibiting CSE also enhanced myogenic tone and depolarized VSM in Shamsham but not IH arteries. Similar results were seen in cerebral arteries. Exogenous H2S dilated and hyperpolarized Shamsham and IH arteries, and this dilation was blocked by iberiotoxin, paxilline, and KCl preconstriction but not glibenclamide or 3-isobutyl-1-methylxanthine. Iberiotoxin enhanced myogenic tone in both groups but more in Shamsham than IH. CSE immunofluorescence was less in the endothelium of IH than in Shamsham mesenteric arteries. Endogenouse H2S dilation was reduced in IH arteries. IH appears to decrease endothelial CSE expression to reduce H2S production, depolarize VSM, and enhance myogenic tone. H2S dilatation and hyperpolarization of VSM in small mesenteric arteries requires BKCa channels.
