on February 26, 2009
Published online before print February 26, 2009, doi: 10.1161/STROKEAHA.108.535435
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Submitted on August 27, 2008
From the Departments of Neurology, OB/GYN & Reproductive Sciences, and Pharmacology (M.J.C., J.S., J.A.G.) and the Vermont Cancer Center (M.M.K.), University of Vermont College of Medicine, Burlington, Vt. * To whom correspondence should be addressed. E-mail: Marilyn.Cipolla{at}uvm.edu.
Background and Purpose—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 in parenchymal arterioles (PA) versus middle cerebral arteries (MCA). Methods—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 nmol/L), TRAM-34 (1.0 µmol/L), and nitro-L-arginine (0.1 mmol/L) were compared in PA and MCA pressurized to 40 mm Hg and 75 mm Hg, respectively. SKCa and IKCa channel mRNA expression was measured using real-time PCR. Results—PA developed greater basal tone than MCA (42±4% versus 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 ischemia and reperfusion, the response to nitric oxide synthase inhibition (NOS) 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 ischemia and reperfusion. However, IKCa channel mRNA expression was 4- to 5-fold greater than SKCa channels. Conclusions—It appears that SKCa and IKCa channel activity diminishes basal tone of PA, but not MCA. The preservation of EDHF responsiveness of PA after ischemia and reperfusion suggests an important role for this vasodilator under conditions when NOS is inhibited.
Revised on October 18, 2008
Accepted on October 20, 2008
SKCa and IKCa Channels, Myogenic Tone, and Vasodilator Responses in Middle Cerebral Arteries and Parenchymal Arterioles. Effect of Ischemia and Reperfusion
Marilyn J. Cipolla PhD*;
Key words: ischemic stroke • parenchymal arterioles • potassium channels • vascular tone
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