Ahmed T, Oliver W, Frank B L, Robinson M J, Wanner A
Am Rev Respir Dis. 1982 Aug;126(2):291-7. doi: 10.1164/arrd.1982.126.2.291.
We used pharmacologic and histologic techniques to investigate the role of mast cells in the mediation of hypoxic pulmonary vasoconstriction in conscious sheep. Breathing a hypoxic gas mixture (13%, 02, 87% nitrogen) caused hypoxic pulmonary vasoconstriction (HPV) with increases in mean pulmonary artery pressure and pulmonary vascular resistance by 97 and 90%, respectively. Intravenous pretreatment with the mast cell membrane stabilizing agent cromolyn sodium (3 mg/kg/min) completely blocked HPV, whereas the H1-histamine receptor antagonist chlorpheniramine, alone or in combination with the H2-receptor antagonist metiamide and the prostaglandin synthetase inhibitor indomethacin, failed to prevent HPV. Cromolyn sodium failed to modify the pulmonary pressor response to infusions of norepinephrine (alpha-agonist), tyramine (catecholamine-releasing agent), and histamine, indicating the specificity of cromolyn sodium action on the mast cells. Electromicroscopic studies of pulmonary perivascular mast cells showed that a 90-min exposure to the hypoxic gas mixture reduced the total number of granules per mast cell to 75% of control. This was blocked by cromolyn sodium pretreatment. We conclude that in conscious sheep], HP[V is initiated by the liberation of a mast cell product (other than histamine) that either directly or indirectly causes pulmonary vasoconstriction.
我们运用药理学和组织学技术，研究了肥大细胞在清醒绵羊低氧性肺血管收缩调节中的作用。吸入低氧气体混合物（13%氧气，87%氮气）会引发低氧性肺血管收缩（HPV），平均肺动脉压和肺血管阻力分别增加97%和90%。用肥大细胞膜稳定剂色甘酸钠（3毫克/千克/分钟）进行静脉预处理可完全阻断HPV，而H1组胺受体拮抗剂氯苯那敏，单独使用或与H2受体拮抗剂甲硫米特及前列腺素合成酶抑制剂吲哚美辛联合使用，均未能预防HPV。色甘酸钠未能改变对去甲肾上腺素（α激动剂）、酪胺（儿茶酚胺释放剂）和组胺输注的肺升压反应，表明色甘酸钠对肥大细胞作用的特异性。对肺血管周围肥大细胞的电镜研究显示，暴露于低氧气体混合物90分钟后，每个肥大细胞的颗粒总数降至对照组的75%。这被色甘酸钠预处理所阻断。我们得出结论，在清醒绵羊中，HPV是由肥大细胞产物（而非组胺）的释放引发的，该产物直接或间接导致肺血管收缩。
