SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion.

SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion.
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DOI:
10.1161/strokeaha.108.535435
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发表时间:
2009-04
期刊:
影响因子:
8.3
通讯作者:
Godfrey JA
Godfrey JA
中科院分区:
医学1区
文献类型:
--
作者:
Cipolla MJ;Smith J;Kohlmeyer MM;Godfrey JA

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The role of SKCa and IKCa channels in myogenic tone and endothelium-derived hyperpolarizing factor (EDHF) responsiveness was investigated under control conditions and after ischemia and reperfusion (I/R) in parenchymal arterioles (PA) vs. middle cerebral arteries (MCA). MCA and PA were dissected from male Wistar rats that were ischemic for 1 hour with 24 hours of reperfusion (n=12) or sham controls (n=12). Basal tone and reactivity to apamin (300 nM), TRAM-34 (1.0 µM) and nitro-L-arginine (L-NNA, 0.1 mM) were compared in PA and MCA pressurized to 40 mmHg and 75 mmHg, respectively. SKCa and IKCa channel mRNA expression was measured using real-time PCR. PA developed greater basal tone than MCA (42±4% vs. 19±3% p<0.01). Addition of apamin and TRAM-34 increased tone of PA by 25±3% and 16±2%, respectively, whereas MCA had no response to either inhibitor. After I/R, the response to NOS inhibition was diminished in PA, whereas EDHF responsiveness was preserved. In addition, stimulated EDHF dilation was partially reversed by apamin and completely reversed by TRAM-34 in both control and ischemic PA. SKCa and IKCa channel mRNA expression was similar in PA and MCA and not altered by I/R. However, IKCa channel mRNA expression was 4–5 fold greater than SKCa channels. It appears that SKCa and IKCa channel activity diminish basal tone of PA, but not MCA. The preservation of EDHF responsiveness of PA after I/R suggests an important role for this vasodilator under conditions when NOS is inhibited.