Cyclooxygenase-2 and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs
Cyclooxygenase-2 and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs
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DOI：
10.1152/japplphysiol.00810.2004
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Pfister, SL
中科院分区：
文献类型：
--
作者：
Fike, CD;Kaplowitz, MR;Pfister, SL
我们的目的是确定环加氧酶 (COX)-2 依赖性代谢物是否会导致慢性缺氧引起的肺动脉高压仔猪中出现的肺血管反应改变。仔猪在室内空气（对照）或缺氧中饲养 3 天。 COX-2 选择性抑制剂 NS-398 对花生四烯酸或乙酰胆碱 (ACh) 反应的影响是在内皮完整和裸露的肺动脉（直径为 100 至 400 微米）中测量的。在 NS-398 存在和不存在的情况下评估肺动脉产生血栓素和前列环素的稳定代谢物。对于完整对照，花生四烯酸的扩张比完整缺氧动脉更大，在任一组的完整动脉中，NS-398均未改变，而在裸露缺氧动脉中，NS-398增强了花生四烯酸的扩张。 NS-398 治疗所有动脉后，ACh 反应在完整的对照动脉中扩张，但在完整和裸露的缺氧动脉中收缩。 NS-398 通过控制肺动脉减少前列环素的产生，并通过缺氧肺动脉减少血栓素的产生。 COX-2依赖性收缩因子，例如血栓素，会导致仔猪在缺氧3天后出现异常的肺动脉反应。
Our objective was to determine whether cyclooxygenase (COX)-2-dependent metabolites contribute to the altered pulmonary vascular responses that manifest in piglets with chronic hypoxia-induced pulmonary hypertension. Piglets were raised in either room air ( control) or hypoxia for 3 days. The effect of the COX-2 selective inhibitor NS-398 on responses to arachidonic acid or acetylcholine (ACh) was measured in endothelium-intact and denuded pulmonary arteries (100- to 400-mum diameter). Pulmonary arterial production of the stable metabolites of thromboxane and prostacyclin was assessed in the presence and absence of NS-398. Dilation to arachidonic acid was greater for intact control than for intact hypoxic arteries, was unchanged by NS-398 in intact arteries of either group, and was augmented by NS-398 in denuded hypoxic arteries. ACh responses, which were dilation in intact control arteries but constriction in intact and denuded hypoxic arteries, were diminished by NS-398 treatment of all arteries. NS-398 reduced prostacyclin production by control pulmonary arteries and reduced thromboxane production by hypoxic pulmonary arteries. COX-2-dependent contracting factors, such as thromboxane, contribute to aberrant pulmonary arterial responses in piglets exposed to 3 days of hypoxia.