Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany.
Institute of Pathology, University of Leipzig, Leipzig, Germany.
Pflugers Arch. 2022 Oct;474(10):1053-1067. doi: 10.1007/s00424-022-02720-9. Epub 2022 Jul 2.
Acute hypoxia impairs left ventricular (LV) inotropic function and induces development of pulmonary edema (PE). Enhanced and uneven hypoxic pulmonary vasoconstriction is an important pathogenic factor of hypoxic PE. We hypothesized that the potent vasodilator relaxin might reduce hypoxic pulmonary vasoconstriction and prevent PE formation. Furthermore, as relaxin has shown beneficial effects in acute heart failure, we expected that relaxin might also improve LV inotropic function in hypoxia. Forty-two rats were exposed over 24 h to normoxia or hypoxia (10% N in O). They were infused with either 0.9% NaCl solution (normoxic/hypoxic controls) or relaxin at two doses (15 and 75 μg kg day). After 24 h, hemodynamic measurements and bronchoalveolar lavage were performed. Lung tissue was obtained for histological and immunohistochemical analyses. Hypoxic control rats presented significant depression of LV systolic pressure by 19% and of left and right ventricular contractility by about 40%. Relaxin did not prevent the hypoxic decrease in LV inotropic function, but re-increased right ventricular contractility. Moreover, hypoxia induced moderate interstitial PE and inflammation in the lung. Contrasting to our hypothesis, relaxin did not prevent hypoxia-induced pulmonary edema and inflammation. In hypoxic control rats, PE was similarly distributed in the apical and basal lung lobes. In relaxin-treated rats, PE index was 35-40% higher in the apical than in the basal lobe, which is probably due to gravity effects. We suggest that relaxin induced exaggerated vasodilation, and hence pulmonary overperfusion. In conclusion, the results show that relaxin does not prevent but rather may aggravate PE formation.
急性缺氧会损害左心室（LV）的变力功能，并导致肺水肿（PE）的发生。增强和不均匀的低氧性肺血管收缩是低氧性 PE 的重要发病因素。我们假设强力血管舒张素松弛素可能会减少低氧性肺血管收缩并防止 PE 的形成。此外，由于松弛素在急性心力衰竭中表现出有益的作用，我们期望松弛素也可能改善缺氧时的 LV 变力功能。42 只大鼠在 24 小时内暴露于常氧或低氧（10%N 在 O 中）。它们分别输注 0.9%NaCl 溶液（常氧/低氧对照组）或两种剂量的松弛素（15 和 75μgkg 天）。24 小时后，进行血流动力学测量和支气管肺泡灌洗。获取肺组织进行组织学和免疫组织化学分析。低氧对照组大鼠的 LV 收缩压显著下降 19%，左、右心室收缩力下降约 40%。松弛素不能防止 LV 变力功能的低氧降低，但重新增加了右心室的收缩力。此外，低氧诱导了中度的间质 PE 和肺部炎症。与我们的假设相反，松弛素并没有预防低氧诱导的肺水肿和炎症。在低氧对照组大鼠中，PE 在肺的顶部和基底叶中分布相似。在松弛素治疗的大鼠中，PE 指数在顶部比在基底叶中高 35-40%，这可能是由于重力的影响。我们认为，松弛素诱导了过度的血管舒张，从而导致肺过度灌注。总之，结果表明，松弛素不仅不能预防，反而可能加重 PE 的形成。
