Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Br J Anaesth. 2011 Jan;106(1):31-7. doi: 10.1093/bja/aeq268. Epub 2010 Oct 8.
The roles of arachidonic acid (AA) metabolites in hypoxia-induced pulmonary vasoconstriction (HPV), a critical physiological mechanism that prevents ventilation/perfusion mismatch, are still incompletely understood.
Pulmonary arterial pressure was measured in ventilated/perfused rat lungs. Isometric tones of rat intralobar pulmonary arteries were also measured, using a myograph.
Hypoxia (Po₂, 3%)-induced pulmonary arterial pressure increases (ΔPAP(hypox)) were stable with blood-mixed perfusate, but decayed spontaneously. ΔPAP(hypox) was inhibited by 29%, 16%, and 28% by the thromboxane A₂ (TXA₂) antagonist SQ-29548, the 5-lipoxygenase inhibitor, MK886, and the leukotriene D₄ antagonist, LY-171883, respectively. The prostacyclin synthase inhibitor tranylcypromine augmented ΔPAP(hypox) by 5%, whereas inhibition of cytochrome P450 did not affect ΔPAP(hypox). Consistently, the TXA₂ analogue U46619 increased ΔPAP(hypox) whereas prostacyclin abolished ΔPAP(hypox). However, leukotriene D₄ had no direct effect on ΔPAP(hypox). In the isolated pulmonary arteries, pretreatment with U46619 was essential to demonstrate hypoxia-induced contraction.
The above results suggest that TXA₂ and cysteinyl leukotrienes, other than leukotriene D₄, are endogenous factors that facilitate HPV in rats. The indispensable role of TXA₂-induced pretone in the HPV of isolated pulmonary arteries indicates that the signal from thromboxane receptors might be a critical component of oxygen sensation mechanisms.
花生四烯酸（AA）代谢产物在缺氧诱导的肺血管收缩（HPV）中的作用仍不完全清楚，HPV 是一种防止通气/灌注不匹配的关键生理机制。
测量通气/灌注大鼠肺中的肺动脉压力。还使用肌动描记器测量大鼠肺叶内肺动脉的等长张力。
混合血液灌注的缺氧（Po₂，3%）诱导的肺动脉压力升高（ΔPAP（hypox））是稳定的，但会自发衰减。血栓烷 A₂（TXA₂）拮抗剂 SQ-29548、5-脂氧合酶抑制剂 MK886 和白三烯 D₄拮抗剂 LY-171883 分别抑制 ΔPAP（hypox）29%、16%和 28%。前列腺素合酶抑制剂曲安西龙使 ΔPAP（hypox）增加 5%，而细胞色素 P450 抑制不影响 ΔPAP（hypox）。一致地，TXA₂类似物 U46619 增加 ΔPAP（hypox），而前列腺素则消除 ΔPAP（hypox）。然而，白三烯 D₄对 ΔPAP（hypox）没有直接影响。在分离的肺动脉中，U46619 的预处理对于证明缺氧诱导的收缩是必需的。
上述结果表明，TXA₂ 和半胱氨酰白三烯，而不是白三烯 D₄，是促进大鼠 HPV 的内源性因素。U46619 预处理在分离肺动脉 HPV 中的不可或缺作用表明，血栓烷受体的信号可能是氧感觉机制的关键组成部分。
