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- W1507224835 abstract "Introduction: Flow-induced vasodilation (FIV) is an important physiological stimulus for regulating vascular tone. A loss of endothelial-dependent FIV is an early indication of endothelial dysfunction. Earlier studies proposed that endothelial inwardly-rectifying K + channels (Kir) are putative flow sensors, but the role of Kir in the regulation of vascular tone is not known. Hypothesis: Kir channels play a key role in FIV. Methods: FIV was assessed in mouse mesenteric arteries isolated from wild type (WT) and Kir2.1 +/- heterozygous mice. Briefly, resistance arteries were isolated, cannulated and pressurized in an organ chamber with glass micropipettes. Preparations were visualized in real time and the inner diameter of the vessels was measured using acquired images. Kir channels in arteries isolated from WT mice were downregulated by a dominant-negative subunit of Kir2.1 or blocked by Ba 2+ . The role of Kir channels in flow-induced release of NO was tested by Diaminorhodamine-4M, NO specific fluorescence dye. Results: Our results show that FIV is significantly inhibited in mesenteric arteries isolated from Kir2.1 +/- mice that have reduced Kir2.1 expression as compared with WT mice (42%±3% relaxation in Kir2.1 +/- vs 94.06%±2.2% in WT mice, n=11, p<0.05). Moreover, blocking Kir channels with Ba 2+ or downregulating its activity with a dominant-negative subunit of Kir2.1 also resulted in significant inhibition of FIV in arteries isolated from WT mice (47%±3% relaxation in the presence of Ba 2+ , 43%±5% in arteries infected with dnKir2.1 vs 94.06%±2.2% in WT n=3, p<0.05). As expected, inhibiting NO release by LNAME, a nitric oxide synthase inhibitor, reduced FIV in WT arteries (39%±5%, n=4, p<0.05), but no effect was observed in arteries isolated from Kir2.1 +/- mice. Furthermore, flow-induced release of NO was significantly reduced (1.5-fold decreased, p<0.05). In contrast, inhibiting Ca 2+ -dependent K + channels (SK/IK) had an additive effect to Kir suppression suggesting that SK/IK and Kir channels regulate FIV by parallel pathways. In conclusion, our results indicate that Kir channels contribute significantly to FIV by regulating NO release." @default.
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- W1507224835 date "2014-11-25" @default.
- W1507224835 modified "2023-09-26" @default.
- W1507224835 title "Abstract 15995: Role of Kir Channels in Flow-Induced Vasodilatation" @default.
- W1507224835 doi "https://doi.org/10.1161/circ.130.suppl_2.15995" @default.
- W1507224835 hasPublicationYear "2014" @default.
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