Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation
Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation
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DOI：
10.1152/ajpheart.00888.2009
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发表时间：
2010-04-01
影响因子：
4.8
通讯作者：
Tune, Johnathan D.
中科院分区：
文献类型：
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作者：
Borbouse, Lena;Dick, Gregory M.;Tune, Johnathan D.
Borbouse L，Dick GM，Payne GA，贝里克ZC，Neeb ZP，Alloosh M，Bratz IN，Sturek M，Tune JD.代谢综合征降低了K+通道对缺血性冠状动脉血管舒张的作用。美国生理学杂志心脏循环生理学298：H1182-H1189，2010年。首次发表于2010年1月29日; doi：10.1152/ajpheart.00888.2009。本研究验证了代谢综合征降低了特定K+通道对冠状动脉反应性充血的相对贡献的假设。研究了钙激活（BKCa）、电压激活（K-V）和ATP依赖性（K-ATP）K+通道。在麻醉的小型Ossabaw猪中进行研究，这些猪饲喂正常维持饮食（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）20周。后一种饮食诱导代谢综合征，增加体重，空腹血糖，总胆固醇和甘油三酯水平。在累积给予BKCa（penitrem A; 10 μ g/kg iv）、K-V（4-氨基吡啶; 0.3 mg/kg iv）和K-ATP（格列本脲; 1 mg/kg iv）通道拮抗剂之前和之后，通过对15 s闭塞的冠状动脉血流反应测定缺血性血管舒张。与瘦肉型猪相比，代谢综合征减少了冠状动脉反应性充血，因为血流债的偿还减少了30%。抑制BKCa通道对瘦猪或代谢综合征猪的反应性充血没有影响。随后抑制KV通道显着降低了流债的偿还（类似于25%）在瘦猪和代谢综合征猪。额外的K-ATP通道阻断进一步减少（类似于45%）流债的偿还瘦，但不是代谢综合征猪。这些数据表明，代谢综合征通过减少K+通道对反应性充血的贡献来损害对心脏缺血的冠状动脉舒张。
Borbouse L, Dick GM, Payne GA, Berwick ZC, Neeb ZP, Alloosh M, Bratz IN, Sturek M, Tune JD. Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation. Am J Physiol Heart Circ Physiol 298: H1182-H1189, 2010. First published January 29, 2010; doi: 10.1152/ajpheart.00888.2009.-This investigation tested the hypothesis that metabolic syndrome decreases the relative contribution of specific K+ channels to coronary reactive hyperemia. Ca2+-activated (BKCa), voltage-activated (K-V), and ATP-dependent (K-ATP) K+ channels were investigated. Studies were conducted in anesthetized miniature 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) for 20 wk. The latter diet induces metabolic syndrome, increasing body weight, fasting glucose, total cholesterol, and triglyceride levels. Ischemic vasodilation was determined by the coronary flow response to a 15-s occlusion before and after cumulative administration of antagonists for BKCa (penitrem A; 10 mu g/kg iv), K-V (4-aminopyridine; 0.3 mg/kg iv) and K-ATP (glibenclamide; 1 mg/kg iv) channels. Coronary reactive hyperemia was diminished by metabolic syndrome as the repayment of flow debt was reduced similar to 30% compared with lean swine. Inhibition of BKCa channels had no effect on reactive hyperemia in either lean or metabolic syndrome swine. Subsequent inhibition of KV channels significantly reduced the repayment of flow debt (similar to 25%) in both lean and metabolic syndrome swine. Additional blockade of K-ATP channels further diminished (similar to 45%) the repayment of flow debt in lean but not metabolic syndrome swine. These data indicate that the metabolic syndrome impairs coronary vasodilation in response to cardiac ischemia via reductions in the contribution of K+ channels to reactive hyperemia.