Department of Anesthesiology, Changzhou No. 2 People's Hospital, Changzhou, Jiangsu 213003, P.R. China.
Mol Med Rep. 2013 Oct;8(4):1263-71. doi: 10.3892/mmr.2013.1645. Epub 2013 Aug 19.
Prostanoids derived from arachidonic acid (AA) have been shown to play a permissive role in the regulation of vascular tone and wall tension. Conventionally, epoxyeicosatrienoic acids (EETs) and prostacyclin have been considered as dilatators, whereas thromboxane (TX) and hydroxyeicosatetraenoic acid (HETE) were considered as vasoconstrictors. However, the role of these prostanoids in the mediation of acute hypoxic pulmonary vasoconstriction is not yet clearly understood. In the present study, the role of prostanoids in the acute hypoxic response in rat isolated intrapulmonary arteries (IPAs) was investigated. Exogenous AA directly caused vasoconstriction, but exerted a significant inhibition on hypoxic vasoconstriction. The vasoconstriction by AA was mediated by the endothelium. AA metabolites from lipoxygenase (LOX) had no effect on vascular tone or hypoxic vasoconstriction. Consistent results from the blockage of cytochrome P450 (CYP) or CYP epoxide hydrolase showed that HETE contributed to endothelium‑independent hypoxic vasoconstriction. EET via epoxygenase exerted no effect on 80 mM KPSS‑induced vessel contraction or hypoxic vasoconstriction. In addition, prostacyclin also failed to inhibit hypoxic pulmonary vasoconstriction (HPV). However, blockage of thromboxane A2/prostanoid (TP) receptors almost eliminated hypoxic vasoconstriction, suggesting the primary role of TP receptors in the regulation of the hypoxic response in rat IPAs. In conclusion, the current data indicate the predominant role of vasoconstrictors instead of dilatators in mediating HPV. These data also highlight a pivotal role for voltage‑independent Ca2+ entry in pulmonary hypoxic response and suggest that modulation of these channels by prostanoids underlies their regulatory mechanisms.
前列腺素衍生自花生四烯酸 (AA)，已被证明在调节血管张力和壁张力方面发挥着许可作用。传统上，环氧化二十碳三烯酸 (EETs) 和前列环素被认为是血管扩张剂，而血栓素 (TX) 和羟二十碳四烯酸 (HETE) 被认为是血管收缩剂。然而，这些前列腺素在介导急性低氧性肺血管收缩中的作用尚不清楚。在本研究中，研究了前列腺素在大鼠离体肺内动脉 (IPAs) 急性低氧反应中的作用。外源性 AA 直接引起血管收缩，但对低氧性血管收缩有显著抑制作用。AA 的血管收缩由内皮介导。来自脂氧合酶 (LOX) 的 AA 代谢物对血管张力或低氧性血管收缩没有影响。细胞色素 P450 (CYP) 或 CYP 环氧化物水解酶阻断的一致结果表明，HETE 有助于内皮非依赖性低氧性血管收缩。环氧合酶的 EET 对 80mM KPSS 诱导的血管收缩或低氧性血管收缩没有影响。此外，前列腺素也不能抑制低氧性肺血管收缩 (HPV)。然而，血栓素 A2/前列腺素 (TP) 受体阻断几乎消除了低氧性血管收缩，表明 TP 受体在调节大鼠 IPA 低氧反应中起主要作用。总之，目前的数据表明，在介导 HPV 方面，收缩剂的作用明显大于扩张剂。这些数据还突出了电压非依赖性 Ca2+内流在肺低氧反应中的关键作用，并表明前列腺素对这些通道的调节在其调节机制中起基础作用。
