Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome
Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome
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DOI：
10.1152/ajpheart.00876.2009
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发表时间：
2010-03-01
影响因子：
4.8
通讯作者：
Tune, Johnathan D.
中科院分区：
文献类型：
--
作者：
Borbouse, Lena;Dick, Gregory M.;Tune, Johnathan D.
Borbouse L，Dick GM，Payne GA，Payne BD，Sundarsen MC，Neeb ZP，Alloosh M，Bratz IN，Sturek M，Tune JD. BKCa通道对局部代谢性冠状血管舒张的作用：代谢综合征的影响Am J Physiol Heart Circ Physiol 298：H966-H973，2010.首次发表于2009年12月31日; doi：10.1152/ajpheart.00876.2009。本研究旨在验证代谢综合征（MetS）患者冠状动脉微血管大电导钙激活钾通道（BKCa）功能受损显著减弱静息和运动诱导心肌耗氧量增加（M（V）超过dotO（2））时心肌氧输送和代谢之间的平衡这一假设。研究在有意识的、长期使用仪器的Ossabaw猪中进行，这些猪喂食正常维持饮食（11%千卡来自脂肪）或过量卡路里的致动脉粥样硬化饮食（43%千卡来自脂肪，2%胆固醇，20%千卡来自果糖），其诱导MetS的许多共同特征。在基线/静息条件下和分级跑台运动期间，在用penitrem A（10 μ g/kg iv）选择性阻断BKCa通道之前和之后收集数据。我们发现运动引起的血压升高在MetS猪中显著升高。未观察到基线心功能或心率差异。MetS的诱导导致冠状静脉PO 2和M（V）相对于dotO（2）的关系平行下移（P < 0.001），伴随着乳酸的显著释放（负乳酸摄取），因为随着运动，M（V）相对于dotO（2）增加（P < 0.005）。在瘦猪或MetS猪中，用penitrem A抑制BKCa通道并没有显著影响血压、心率或冠状静脉PO 2与M（V）和dotO（2）之间的关系。这些数据表明，BKCa通道不需要在生理（瘦）或病理生理（MetS）条件下的冠状动脉血流的局部代谢控制。因此，BKCa通道功能的减弱并不影响代谢综合征患者心肌氧供需平衡的受损。
Borbouse L, Dick GM, Payne GA, Payne BD, Svendsen MC, Neeb ZP, Alloosh M, Bratz IN, Sturek M, Tune JD. Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome. Am J Physiol Heart Circ Physiol 298: H966-H973, 2010. First published December 31, 2009; doi:10.1152/ajpheart.00876.2009.-This investigation was designed to examine the hypothesis that impaired function of coronary microvascular large-conductance Ca2+-activated K+ (BKCa) channels in metabolic syndrome (MetS) significantly attenuates the balance between myocardial oxygen delivery and metabolism at rest and during exercise-induced increases in myocardial oxygen consumption (M(V) over dotO(2)). Studies were conducted in conscious, chronically instrumented Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) that induces many common features of MetS. Data were collected under baseline/resting conditions and during graded treadmill exercise before and after selective blockade of BKCa channels with penitrem A (10 mu g/kg iv). We found that the exercise-induced increases in blood pressure were significantly elevated in MetS swine. No differences in baseline cardiac function or heart rate were noted. Induction of MetS produced a parallel downward shift in the relationship between coronary venous PO2 and M(V) over dotO(2) (P < 0.001) that was accompanied by a marked release of lactate (negative lactate uptake) as M(V) over dotO(2) was increased with exercise (P < 0.005). Inhibition of BKCa channels with penitrem A did not significantly affect blood pressure, heart rate, or the relationship between coronary venous PO2 and M(V) over dotO(2) in lean or MetS swine. These data indicate that BKCa channels are not required for local metabolic control of coronary blood flow under physiological (lean) or pathophysiological (MetS) conditions. Therefore, diminished function of BKCa channels does not contribute to the impairment of myocardial oxygen-supply demand balance in MetS.