Oka Masahiko, Homma Noriyuki, McMurtry Ivan F
Cardiovascular Pulmonary Research Laboratory, University of Colorado at Denver, Health Sciences Center, Denver, Colorado, USA.
Methods Enzymol. 2008;439:191-204. doi: 10.1016/S0076-6879(07)00415-6.
There is current controversy regarding whether vasoconstriction plays a significant role in the elevated pressure of severe, advanced stages of pulmonary hypertension. Results of acute vasodilator testing using conventional vasodilators in such patients suggest there is only a minor contribution of vasoconstriction. However, there is a possibility that these results may underestimate the contribution of vasoconstriction because the most effective vasodilators have not yet been tested. This issue has not been addressed even experimentally, due mainly to a lack of appropriate animal models. A few animal models that mimic the pathology of human severe pulmonary hypertension more closely (i.e., development of occlusive neointimal lesions in small pulmonary arteries/arterioles) have been introduced, including rat models of left lung pneumonectomy plus monocrotaline injection and vascular endothelial growth factor inhibition plus exposure to chronic hypoxia. We have observed that Rho kinase inhibitors, a novel class of potent vasodilators, reduce the high pulmonary artery pressure of these models acutely and markedly, suggesting that vasoconstriction can significantly be involved in pulmonary hypertension with severely remodeled (occluded) pulmonary vessels. This chapter describes methods used for evaluation of the involvement of Rho kinase-mediated vasoconstriction in rat models of pulmonary hypertension.
关于血管收缩在重度晚期肺动脉高压升高的压力中是否起重要作用，目前存在争议。在此类患者中使用传统血管扩张剂进行急性血管扩张试验的结果表明，血管收缩的作用很小。然而，这些结果有可能低估了血管收缩的作用，因为尚未测试最有效的血管扩张剂。这个问题甚至在实验中也没有得到解决，主要原因是缺乏合适的动物模型。已经引入了一些更接近模拟人类重度肺动脉高压病理（即小肺动脉/小动脉中闭塞性新内膜病变的发展）的动物模型，包括左肺肺叶切除加野百合碱注射的大鼠模型以及血管内皮生长因子抑制加慢性缺氧暴露的大鼠模型。我们观察到，Rho激酶抑制剂是一类新型强效血管扩张剂，可急性且显著降低这些模型的高肺动脉压力，这表明血管收缩可能在伴有严重重塑（闭塞）肺血管的肺动脉高压中起重要作用。本章描述了用于评估Rho激酶介导的血管收缩在大鼠肺动脉高压模型中的作用的方法。
