Packer C S, Bennie R E, Powell D R, Rhoades R A
Department of Physiology/Biophysics, Indiana University School of Medicine, Indianapolis 46202.
Respir Physiol. 1994 May;96(2-3):213-29. doi: 10.1016/0034-5687(94)90128-7.
The purpose of this study was to determine if neonatal hypoxia alters pulmonary arterial smooth muscle (PASM) function in young adult rats. One day old rats were made hypoxic (FIO2 = 0.1) for 5 days, then maintained under normoxic conditions until young adulthood (45-50 days). Age-matched rats were used as controls. Body weight, hematocrit, dry lung weight, and right to left heart ratios were measured. Reactivity and/or responsiveness of rings of main right and left pulmonary artery of the adult to various agonists, including high K+ (80 mM KCl), norepinephrine (NE), serotonin (5HT), adenosine (AD), and acute in vitro hypoxic vasoconstriction were assessed. Isometric force production was normalized to calculated tissue cross-sectional area (N/cm2). Maximum force production (PO) in response to 80 mM KCl for isolated rings from the hypoxic group was significantly less than for controls. Isometric force production in response to NE or to 5HT was also lower in the hypoxic group although the difference was significant for 5HT only when the endothelium was rendered non-functional. When the endothelium was intact, arterial rings from experimental animals relaxed at low doses of adenosine (10(-8) M to 10(-5) M), while control arterial muscle showed no response at these concentrations. The mean dose-response curve for NE from preparations with intact endothelium from experimental animals was significantly lower than that for the control animals, at least at doses greater than 10(-7) M. To mimic acute hypoxic pulmonary vasoconstriction, isolated rings of the main right and left pulmonary artery were precontracted with either 30 mM KCl or 2.5 x 10(-7) M NE and then made hypoxic by lowering muscle bath PO2 to 30-40 mmHg. In conclusion there was no difference in the hypoxic response per se between arterial rings from experimental animals and controls. However, maximum reactivity to high potassium stimulation and to norepinephrine stimulation is decreased in pulmonary arterial smooth muscle of adult animals that had been exposed to 5 days of hypoxia as neonates.
本研究的目的是确定新生儿期缺氧是否会改变年轻成年大鼠的肺动脉平滑肌（PASM）功能。将出生一天的大鼠置于低氧环境（FIO2 = 0.1）中5天，然后在常氧条件下饲养至年轻成年期（45 - 50天）。以年龄匹配的大鼠作为对照。测量体重、血细胞比容、肺干重以及右心与左心比值。评估成年大鼠主肺动脉左右分支环对各种激动剂的反应性和/或反应，这些激动剂包括高钾（80 mM KCl）、去甲肾上腺素（NE）、5 - 羟色胺（5HT）、腺苷（AD），以及急性体外低氧性血管收缩。将等长力产生值根据计算出的组织横截面积进行标准化（N/cm²）。缺氧组分离环对80 mM KCl反应的最大力产生（PO）显著低于对照组。缺氧组对NE或5HT的等长力产生也较低，不过仅当内皮失去功能时，对5HT的差异才具有统计学意义。当内皮完整时，实验动物的动脉环在低剂量腺苷（10⁻⁸ M至10⁻⁵ M）作用下舒张，而对照动脉平滑肌在这些浓度下无反应。至少在剂量大于10⁻⁷ M时，实验动物完整内皮制剂中NE的平均剂量 - 反应曲线显著低于对照动物。为模拟急性低氧性肺血管收缩，将主肺动脉左右分支的分离环先用30 mM KCl或2.5×10⁻⁷ M NE预收缩，然后通过将肌肉浴PO₂降至30 - 40 mmHg使其处于低氧状态。总之，实验动物和对照动物的动脉环在低氧反应本身方面没有差异。然而，成年动物若在新生儿期曾经历5天缺氧，其肺动脉平滑肌对高钾刺激和去甲肾上腺素刺激的最大反应性会降低。
