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                <text>Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins.</text>
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                <text>coronary arteris; microcirculation; myogenic tone; nicotinamide adenine dinucleotide; voltage-gated potassium channels</text>
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                <text>Ohanyan V;Raph SM;Dwenger MM;Hu X;Pucci T;Mack GD;Moore IJB;Chilian WM;Bhatnagar A;Nystoriak MA</text>
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                <text>Rationale: Voltage-gated potassium (Kv) channels in vascular smooth muscle are essential for coupling myocardial blood flow (MBF) with the metabolic demand of the  heart. These channels consist of a transmembrane pore domain that associates with  auxiliary Kvβ1 and Kvβ2 proteins, which differentially regulate Kv function in  excitable cells. Nonetheless, the physiological role of Kvβ proteins in regulating  vascular tone and metabolic hyperemia in the heart remains unknown. Objective: To  test the hypothesis that Kvβ proteins confer oxygen sensitivity to vascular tone and  are required for regulating blood flow in the heart. Methods and Results: Mice  lacking Kvβ2 subunits exhibited suppressed MBF, impaired cardiac contractile  performance, and failed to maintain elevated arterial blood pressure in response to  catecholamine-induced stress. In contrast, ablation of Kvβ1.1 reduced cardiac  workload, modestly elevated MBF, and preserved cardiac function during stress  compared with wild type mice. Coronary arteries isolated from Kvβ2-/-, but not  Kvβ1.1-/-, mice, had severely blunted vasodilation to hypoxia when compared with  arteries from wild type mice. Moreover, vasodilation of small diameter coronary and  mesenteric arteries due to L-lactate, a biochemical marker of reduced tissue  oxygenation and anaerobic metabolism, was significantly attenuated in vessels  isolated from Kvβ2-/- mice. Inducible enhancement of the Kvβ1:Kvβ2 ratio in Kv1  channels of arterial smooth muscle abolished L-lactate-induced vasodilation and  suppressed the relationship between MBF and cardiac workload.Conclusions: The Kvβ  proteins differentially regulate vascular tone and myocardial blood flow, whereby  Kvβ2 promotes and Kvβ1.1 inhibits oxygen-dependent vasodilation and augments blood  flow upon heightened metabolic demand.</text>
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                <text>&lt;a href="http://doi.org/10.1161/CIRCRESAHA.120.317715" target="_blank" rel="noreferrer noopener"&gt;10.1161/CIRCRESAHA.120.317715&lt;/a&gt;</text>
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                <text>Circulation Research</text>
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