Stevens T, Morris K, McMurtry I F, Zamora M, Tucker A
Department of Physiology, Colorado State University, Fort Collins 80523.
J Appl Physiol (1985). 1993 Apr;74(4):1905-10. doi: 10.1152/jappl.1993.74.4.1905.
Endotoxin decreases pulmonary vascular reactivity. Because tumor necrosis factor-alpha (TNF-alpha) is a primary mediator of endotoxemia, we tested whether TNF-alpha altered pulmonary vascular reactivity in conscious adult female rats. Osmotic pumps were implanted intraperitoneally, and low-dose TNF-alpha (62 micrograms, TNF62; n = 7), high-dose TNF-alpha (> or = 250 micrograms, TNF250; n = 5), or saline (n = 5) was administered for 2 wk. Pulmonary pressor responses to 14% O2 and angiotensin II (ANG II, 0.0206 micrograms/min for 10 min) were measured without (day 13) or after (day 14) administration of nitro-L-arginine (4.4 mg/kg iv), an inhibitor of endothelium-derived relaxing factor (EDRF). TNF-alpha administration slightly decreased (P < or = 0.08) baseline pulmonary arterial pressure in TNF250 rats and decreased (P < or = 0.05) hypoxia- and ANG II-induced constrictions in TNF62 and TNF250 rats. Whereas nitro-L-arginine potentiated (P < or = 0.05) pressure responses in control rats, it had no effect on hypoxic responses in TNF-alpha-treated rats. Nitro-L-arginine increased (P < or = 0.05) ANG II-induced vasoconstriction in TNF-alpha-treated rats, but the pulmonary arterial pressure response was still lower (P < or = 0.05) in TNF250 than in control and TNF62 rats. These results suggest that chronic TNF-alpha decreases 1) pulmonary vascular reactivity in the intact rat, 2) hypoxic pulmonary vasoconstriction by a mechanism that is independent of EDRF, and 3) ANG II-induced constriction by a mechanism that is partly EDRF dependent.
内毒素可降低肺血管反应性。由于肿瘤坏死因子-α（TNF-α）是内毒素血症的主要介质，我们测试了TNF-α是否会改变成年雌性清醒大鼠的肺血管反应性。将渗透泵植入腹腔内，给予低剂量TNF-α（62微克，TNF62；n = 7）、高剂量TNF-α（≥250微克，TNF250；n = 5）或生理盐水（n = 5），持续2周。在给予内皮源性舒张因子（EDRF）抑制剂硝基-L-精氨酸（4.4毫克/千克静脉注射）之前（第13天）或之后（第14天），测量对14%氧气和血管紧张素II（ANG II，0.0206微克/分钟，持续10分钟）的肺升压反应。给予TNF-α使TNF250大鼠的基线肺动脉压略有降低（P≤0.08），并使TNF62和TNF250大鼠中缺氧和ANG II诱导的收缩反应降低（P≤0.05）。虽然硝基-L-精氨酸增强了（P≤0.05）对照大鼠的压力反应，但对TNF-α处理的大鼠的缺氧反应没有影响。硝基-L-精氨酸增加了（P≤0.05）TNF-α处理的大鼠中ANG II诱导的血管收缩，但TNF250大鼠的肺动脉压反应仍低于对照和TNF62大鼠（P≤0.05）。这些结果表明，慢性TNF-α可降低1）完整大鼠的肺血管反应性，2）通过独立于EDRF的机制降低缺氧性肺血管收缩，以及3）通过部分依赖EDRF的机制降低ANG II诱导的收缩。
