期刊
EUROPEAN RESPIRATORY JOURNAL
卷 22, 期 4, 页码 596-601出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.03.00027903
关键词
precision cut lung slices; pulmonary hypertension; reactive oxygen species; substance P; vascular remodelling
Substance P (SP) levels have been reported to be elevated in animal models of pulmonary hypertension (PH) and chronic administration of SP has been shown to induce PH. In the present study, the role of reactive oxygen species (ROS) as mediators of SP-induced vascular remodelling and PH was analysed. Vascular remodelling was induced in precision cut lung slices by treatment with [Sar(9),Met(11)(O-2)]-SP and by hypoxia. Functional analyses were used to study the chronic [Sar(9),Met(11)(O-2)]-SP-mediated effects on proliferation and generation of ROS, which is involved in the pathogenesis of PH. The nonpeptide NK-1 receptor antagonist CP 96345 was used to block [Sar(9),Met(11)(O-2)]-SP effects. ROS generation and proliferation was assayed by the dichloroflourescein-diacetate method and incorporation of 5-Bromo-2'-Deoxyuridine, respectively. ROS generation was induced by either 1% oxygen (5.8-fold) or [Sar(9),Met(11)(O-2)]-SP (8-fold) in normoxia in the alveolar region. [Sar(9),Met(11)(O-2)]-SP did not further elevate ROS levels in hypoxia, suggesting an oxygen-dependent mechanism. High ROS levels stabilised hypoxia inducible factor-la and induced proliferation in small vessels (4.3-fold in hypoxia and [Sar(9),Met(11)(O-2)]-SP). Both ROS generation and proliferation were blocked in the presence of CP 96345, nitroblue-tetrazolium, N-acetylcysteine- and diphenylene-iodonium. The results presented in this study indicate a role of SP in proliferative events associated with vascular remodelling in pulmonary hypertension.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据