Frantz E G, Schreiber M D, Soifer S J
Cardiovascular Research Institute, University of California, San Francisco 94143.
J Dev Physiol. 1988 Dec;10(6):555-65.
Hypoxia-induced pulmonary hypertension may be mediated by leukotrienes. Pulmonary mast cells produce leukotrienes, histamine and prostaglandin D2, and degranulate in response to hypoxia. Cromolyn sodium, a mast cell membrane stabilizing agent, may prevent hypoxia-induced mast cell degranulation. To investigate the role of mast cell products in hypoxia-induced pulmonary hypertension, we studied the haemodynamic responses to alveolar hypoxia before and during an intravenous infusion of 3-5 mg/min per kg of cromolyn sodium in 6 chronically instrumented, spontaneously breathing lambs. Since there are age-dependent differences in the response of the pulmonary circulation to some mast cell products, we studied the effects of cromolyn sodium on hypoxia-induced pulmonary hypertension in newborn (4-7 days) and young lambs (15-18 days). During alveolar hypoxia, mean pulmonary arterial pressure increased by 68% (P less than 0.05) and 59% (P less than 0.05) in the newborn and young lambs, respectively. With alveolar hypoxia during cromolyn sodium infusion, mean pulmonary arterial pressure increased by 71% (P less than 0.05) and 42% (P less than 0.05) in the newborn and young lambs, respectively. Cromolyn sodium did blunt the hypoxia-induced release of histamine into the circulation. Because hypoxia-induced pulmonary hypertension was not inhibited by cromolyn sodium in either age group, mast cell products are not important mediators of hypoxia-induced pulmonary hypertension.
缺氧诱导的肺动脉高压可能由白三烯介导。肺肥大细胞产生白三烯、组胺和前列腺素D2，并在缺氧时脱颗粒。色甘酸钠是一种肥大细胞膜稳定剂，可能会阻止缺氧诱导的肥大细胞脱颗粒。为了研究肥大细胞产物在缺氧诱导的肺动脉高压中的作用，我们在6只长期植入仪器、自主呼吸的羔羊中，研究了静脉输注3 - 5毫克/分钟每千克色甘酸钠之前和期间对肺泡缺氧的血流动力学反应。由于肺循环对某些肥大细胞产物的反应存在年龄依赖性差异，我们研究了色甘酸钠对新生羔羊（4 - 7天）和幼龄羔羊（15 - 18天）缺氧诱导的肺动脉高压的影响。在肺泡缺氧期间，新生羔羊和幼龄羔羊的平均肺动脉压分别升高了68%（P小于0.05）和59%（P小于0.05）。在输注色甘酸钠期间进行肺泡缺氧时，新生羔羊和幼龄羔羊的平均肺动脉压分别升高了71%（P小于0.05）和42%（P小于0.05）。色甘酸钠确实抑制了缺氧诱导的组胺释放到循环中。因为在两个年龄组中色甘酸钠都没有抑制缺氧诱导的肺动脉高压，所以肥大细胞产物不是缺氧诱导的肺动脉高压的重要介质。
