Activation of barium-sensitive inward rectifier potassium channels mediates remote dilation of coronary arterioles

Article

关键词: CA2+-ACTIVATED K+ CHANNELS;    SMOOTH-MUSCLE;    MEMBRANE HYPERPOLARIZATION;    ENDOTHELIAL-CELLS;    NITRIC-OXIDE;    BLOOD-FLOW;    RESISTANCE;    ADENOSINE;    RESPONSES;   

DOI  :  10.1161/hc4001.098053

来源: SCIE

【 摘 要 】

Background-Conducted vasodilation seems to be critical for the functional distribution of blood flow in the skeletal muscle microcirculation. However, this vasoregulatory phenomenon has not been documented in the coronary microcirculation, and its underlying mechanism remains elusive. Because potassium ions are potent metabolic vasodilators in the heart, by activating vascular inward rectifier K+ (K-ir) channels, we tested the hypothesis that coronary arterioles exhibit remote vasodilation through activation of this type of channel. Methods and Results-Porcine coronary arterioles were isolated, cannulated, and pressurized for in vitro study. Vessels dilated concentration-dependently to extraluminal KCI (5 to 20 mmol/L), bradykinin, adenosine, pinacidil, and sodium nitroprusside. A K-ir channel blocker, BaCl2 (30 mu mol/L), inhibited vasodilatory responses to KCl and bradykinin but not to adenosine, pinacidil, or nitroprusside. In a flow chamber, localized administration of bradykinin, adenosine, and KCl to the downstream end of the arterioles caused approximate to 80% dilation at the site of drug application (local site) and also produced 30% to 60% dilation at the upstream end of arterioles (remote site). Nitroprusside produced a similar dilation at the local site but failed to initiate remote vasodilation. In the presence of Ba2+, adenosine still dilated the local site, but the local dilations to bradykinin and KCI and the remote dilations to adenosine, bradykinin, and KCI were inhibited. Conclusions-We demonstrated that some modes of local vasodilation can be conducted to remote sites in coronary arterioles and that local and remote dilations can occur through different vasodilatory mechanisms. Activation of K-ir channels seems critical for some agonist-induced local vasodilations and also for the initiation and/or transmission of signals causing remote vasodilation.

【 授权许可】

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