Effects of hypoxia on isometric force, intracellular Ca(2+), pH, and energetics in porcine coronary artery.
Effects of hypoxia on isometric force, intracellular Ca(2+), pH, and energetics in porcine coronary artery.
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DOI：
10.1161/01.res.86.8.862
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发表时间：
2000-04
影响因子：
20.1
通讯作者：
Shunichi Shimizu;P. S. Bowman;G. D. Thorne;Richard J. Paul
中科院分区：
文献类型：
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作者：
Shunichi Shimizu;P. S. Bowman;G. D. Thorne;Richard J. Paul
当暴露在低氧条件下时，冠状动脉扩张，这是一种重要的保护性反应。尽管血管对氧气的敏感性已有很好的文献记载，但其机制尚不确定。为了进一步研究冠脉氧感应的机制，我们通过测量低氧对能量、[Ca(2+)](I)、K(+)通道功能和pH(I)的影响来检验主要的假说。低氧可松弛KCl或U46619刺激的猪冠状动脉。放松的程度取决于刺激的程度和种类。用Fura-2-AM和比率荧光技术测定去内皮动脉的[Ca(2+)](I)。在较低的刺激水平下，低氧降低了肌力和[Ca(2+)](I)。抑制剂研究表明，K(Ca)和K(ATP)通道不参与缺氧的松弛，而K(V)通道可能起到很小的作用。尽管低氧导致心肌细胞[Ca(2+)](I)降低，但在高水平刺激下，[Ca(2+)](I)不变或升高。尽管乳酸含量显著增加，pH(I)(用比率荧光染料BCECF测量)也几乎没有受到缺氧的影响。用分析等速电泳法测量冷冻夹闭动脉的磷酸原和代谢物分布表明，低氧使乳酸含量增加了4倍，而磷酸肌酸减少到对照组的60%。低氧对ATP和P(I)无明显影响。有趣的是，根据无氧乳酸产生的测量，低氧条件下的额外刺激增加了力量，但并没有增加ATP的利用。因此，令人惊讶的是，在低氧条件下，力量维持的经济性增加了。在猪冠状动脉中，Ca(2+)依赖和更重要的是Ca(2+)非依赖性机制都参与了缺氧性血管扩张。对于后者，不能调用涉及ATP、[Ca(2+)](I)、pH(I)或P(I)的机制。这种新的氧传感机制包括降低对Ca(2+)的敏感性。
When exposed to hypoxic conditions, coronary arteries dilate, which is an important protective response. Although vessel sensitivity to oxygen is well documented, the mechanisms are not known with certainty. To further characterize the mechanisms of oxygen sensing in the coronary artery, we tested the major classes of hypotheses by measuring the effects of hypoxia on energetics, [Ca(2+)](i), K(+) channel function, and pH(i). Hypoxia relaxes porcine coronary arteries stimulated with either KCl or U46619. The extent of relaxation is dependent on both the degree and kind of stimulation. [Ca(2+)](i) was measured in endothelium-denuded arteries using fura 2-AM and ratiometric fluorescent techniques. At lower stimulus levels, hypoxia decreased both force and [Ca(2+)](i). Inhibitor studies suggest that K(Ca) and K(ATP) channels are not involved in the hypoxic relaxation, whereas K(V) channels may play a minor role, if any. Despite the hypoxia-mediated decrease in force, [Ca(2+)](i) was unchanged or increased at high levels of stimulation. Despite a marked increase in lactate content, pH(i) (measured with the ratiometric fluorescent dye BCECF) was also little affected by hypoxia. Measurement of the phosphagen and metabolite profile of freeze-clamped arteries with analytical isotachophoresis indicated that hypoxia increased lactate content by 4-fold and decreased phosphocreatine to 60% of control. However, neither ATP nor P(i) was affected by hypoxia. Interestingly, additional stimulation under hypoxia increased force but not ATP utilization, as estimated from measurements of anaerobic lactate production. Thus, surprisingly, the economy of force maintenance is increased under hypoxia. In porcine coronary artery, both Ca(2+)-dependent and, importantly, Ca(2+)-independent mechanisms are involved in hypoxic vasodilatation. For the latter, mechanisms involving either ATP, [Ca(2+)](i), pH(i), or P(i) cannot be invoked. This novel oxygen sensing mechanism involves a decreased Ca(2+) sensitivity.