SK Ca and IK Ca channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles effect of ischemia and reperfusion

Abstract

Background and Purpose - The role of SK Ca and IK Ca channels in myogenic tone and endothelium-derived hyperpolar-izing 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. SK Ca and IK Ca 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. SK Ca and IK Ca channel mRNA expression was similar in PA and MCA and not altered by ischemia and reperfusion. However, IK Ca channel mRNA expression was 4- to 5-fold greater than SK Ca channels. Conclusions - It appears that SK Ca and IK Ca 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. © 2009 American Heart Association, Inc.