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<a href="http://doi.org/10.1161/CIRCRESAHA.120.317715" target="_blank" rel="noreferrer noopener">http://doi.org/10.1161/CIRCRESAHA.120.317715</a>
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1524-4571 0009-7330
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Update Year & Number
February 2021 List
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Integrative Medical Sciences
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Title
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Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins.
Date
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2021
2021-01-27
Subject
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coronary arteris; microcirculation; myogenic tone; nicotinamide adenine dinucleotide; voltage-gated potassium channels
Creator
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Ohanyan V;Raph SM;Dwenger MM;Hu X;Pucci T;Mack GD;Moore IJB;Chilian WM;Bhatnagar A;Nystoriak MA
Description
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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.
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<a href="http://doi.org/10.1161/CIRCRESAHA.120.317715" target="_blank" rel="noreferrer noopener">10.1161/CIRCRESAHA.120.317715</a>
Format
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journalArticle
Publisher
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Circulation Research
2021
Bhatnagar A
Chilian WM
Circulation research
coronary arteris
Department of Integrative Medical Sciences
Dwenger MM
February 2021 List
Hu X
journalArticle
Mack GD
Microcirculation
Moore IJB
myogenic tone
NEOMED College of Medicine
nicotinamide adenine dinucleotide
Nystoriak MA
Ohanyan V
Pucci T
Raph SM
voltage-gated potassium channels