Soma S, Takahashi H, Muramatsu M, Oka M, Fukuchi Y
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Am J Respir Cell Mol Biol. 1999 Apr;20(4):620-30. doi: 10.1165/ajrcmb.20.4.3356.
To clarify the roles of two different endothelin (ET) receptors in the pulmonary vasculature, the localization and distribution of endothelin-A (ETA) and ETB receptors were investigated in rat lung under normal and hypoxic conditions by an immunohistochemical method. We also carried out in situ hybridization for ETB receptor. In normal rats, ETA receptor is localized in the media of the pulmonary artery and vein with predominant distribution in such proximal segments as elastic arteries and large muscular arteries. ETB receptor is expressed in the intima and media of pulmonary vessels. The distribution of ETB receptor in the media predominates in the distal segments of the pulmonary artery, whereas its distribution in the intima is greater in the proximal segments. Immunoreactivity for ETA receptor increases in the media of the distal segments of the pulmonary artery after exposure to hypobaric hypoxia. Semiquantitative evaluation showed immunoreactivity for ETA receptor in the pulmonary arteries accompanying the terminal bronchioles, respiratory bronchioles, and alveolar ducts to be increased by 2.5-, 5-, and 20-fold after 14 d exposure to hypoxia, respectively. The messenger RNA and immunoreactivity for ETB receptor increased significantly in the intima of the distal segments of pulmonary artery after 7 and 14 d exposure to hypoxia. These results suggest that the vasoconstrictive effects of ET-1 are exerted mainly through ETA receptor in the proximal segments of the pulmonary artery and vein, whereas its effects in the distal segments are mediated by ETA and ETB receptors in normal rats. ETA receptors that increase in resistance arteries after exposure to hypoxia appear to play an important role in the vascular remodeling associated with hypoxic pulmonary hypertension. Because ETB receptors in the endothelium mediate ET-1-induced vasodilatory effects, the increase in endothelial ETB receptors may counteract the development of hypoxic pulmonary hypertension.
为阐明两种不同的内皮素（ET）受体在肺血管系统中的作用，采用免疫组织化学方法研究了正常和低氧条件下大鼠肺组织中内皮素A（ETA）受体和ETB受体的定位与分布。我们还对ETB受体进行了原位杂交。在正常大鼠中，ETA受体定位于肺动脉和肺静脉的中膜，在弹性动脉和大肌性动脉等近端节段分布占主导。ETB受体在肺血管的内膜和中膜表达。ETB受体在中膜的分布在肺动脉远端节段占优势，而其在内膜的分布在近端节段更多。暴露于低压低氧后，肺动脉远端节段中膜的ETA受体免疫反应性增加。半定量评估显示，暴露于低氧14天后，终末细支气管、呼吸性细支气管和肺泡管伴行肺动脉中的ETA受体免疫反应性分别增加了2.5倍、5倍和20倍。暴露于低氧7天和14天后，肺动脉远端节段内膜中ETB受体的信使核糖核酸和免疫反应性显著增加。这些结果表明，ET-1的血管收缩作用主要通过肺动脉和肺静脉近端节段的ETA受体发挥，而在正常大鼠中，其在远端节段的作用由ETA和ETB受体介导。暴露于低氧后阻力动脉中增加的ETA受体似乎在与低氧性肺动脉高压相关的血管重塑中起重要作用。由于内皮中的ETB受体介导ET-1诱导的血管舒张作用，内皮ETB受体的增加可能会抵消低氧性肺动脉高压的发展。
