Reyes Roberto V, Castillo-Galán Sebastián, Hernandez Ismael, Herrera Emilio A, Ebensperger Germán, Llanos Aníbal J
Unidad de Fisiología y Fisiopatología Perinatal, Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
International Center for Andean Studies, Universidad de Chile, Santiago, Chile.
Front Physiol. 2018 May 7;9:486. doi: 10.3389/fphys.2018.00486. eCollection 2018.
The pulmonary arteries are exquisitely responsive to oxygen changes. They rapidly and proportionally contract as arterial PO decrease, and they relax as arterial PO is re-established. The hypoxic pulmonary vasoconstriction (HPV) is intrinsic since it does not require neural or endocrine factors, as evidenced in isolated vessels. On the other hand, pulmonary arteries also respond to sustained hypoxia with structural and functional remodeling, involving growth of smooth muscle medial layer and later recruitment of adventitial fibroblasts, secreted mitogens from endothelium and changes in the response to vasoconstrictor and vasodilator stimuli. Hypoxic pulmonary arterial vasoconstriction and remodeling are relevant biological responses both under physiological and pathological conditions, to explain matching between ventilation and perfusion, fetal to neonatal transition of pulmonary circulation and pulmonary artery over-constriction and thickening in pulmonary hypertension. Store operated channels (SOC) and receptor operated channels (ROC) are plasma membrane cationic channels that mediate calcium influx in response to depletion of internal calcium stores or receptor activation, respectively. They are involved in both HPV and pathological remodeling since their pharmacological blockade or genetic suppression of several of the Stim, Orai, TRP, or ASIC proteins in SOC or ROC complexes attenuate the calcium increase, the tension development, the pulmonary artery smooth muscle proliferation, and pulmonary arterial hypertension. In this Mini Review, we discussed the evidence obtained in animal models, at the level of isolated organ or cells of pulmonary arteries, and we identified and discussed the questions for future research needed to validate these signaling complexes as targets against pulmonary hypertension.
肺动脉对氧气变化极为敏感。随着动脉血氧分压（PO）降低，它们会迅速且成比例地收缩；而当动脉血氧分压恢复时，它们则会舒张。低氧性肺血管收缩（HPV）是内在性的，因为它不需要神经或内分泌因素，这在离体血管中得到了证实。另一方面，肺动脉对持续缺氧也会产生结构和功能重塑反应，包括平滑肌中层的生长以及随后外膜成纤维细胞的募集、内皮细胞分泌的有丝分裂原，以及对血管收缩剂和血管舒张剂刺激反应的改变。低氧性肺动脉血管收缩和重塑在生理和病理条件下都是相关的生物学反应，可用于解释通气与灌注的匹配、肺循环从胎儿到新生儿的转变，以及肺动脉高压时肺动脉过度收缩和增厚的现象。储存操纵性通道（SOC）和受体操纵性通道（ROC）是质膜阳离子通道，分别介导因细胞内钙储存耗竭或受体激活而引起的钙内流。它们参与HPV和病理重塑过程，因为对SOC或ROC复合物中几种Stim、Orai、TRP或ASIC蛋白进行药理学阻断或基因抑制，会减弱钙增加、张力发展、肺动脉平滑肌增殖以及肺动脉高压。在本综述中，我们讨论了在动物模型、肺动脉离体器官或细胞水平上获得的证据，并确定和讨论了未来研究中需要解决的问题，以验证这些信号复合物作为抗肺动脉高压靶点的有效性。
