| Title | Oestradiol ameliorates monocrotaline pulmonary hypertension via NO, prostacyclin and endothelin-1 pathways |
| Authors | Yuan, Ping Wu, Wen-Hui Gao, Lan Zheng, Ze-Qi Liu, Dong Mei, Han-Ying Zhang, Zhuo-Li Jing, Zhi-Cheng |
| Affiliation | Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Cardiopulm Circulat, Shanghai, Peoples R China. Beijing Univ, Hlth Sci Ctr, Beijing Univ Hosp 1, Dept Rheumatol, Beijing 100871, Peoples R China. Nanchang Univ, Affiliated Hosp 1, Dept Cardiol, Nanchang, Jiangxi, Peoples R China. Fu Wai Hosp, PUMC&CAMS, Dept Cardiol, Beijing, Peoples R China. Fu Wai Hosp PUMC&CAMS 167, Dept Cardiol, Beilishi Rd, Beijing 100037, Peoples R China. |
| Keywords | 17 beta-oestradiol metabolic enzymes oestrogen receptors pulmonary hypertension ARTERIAL-HYPERTENSION NITRIC-OXIDE REPLACEMENT THERAPY ESTROGEN DISEASE RATS ENOS EXPRESSION MANAGEMENT INHIBITOR |
| Issue Date | 2013 |
| Publisher | european respiratory journal |
| Citation | EUROPEAN RESPIRATORY JOURNAL.2013,41,(5),1116-1125. |
| Abstract | Pulmonary hypertension continues to be a serious clinical problem with high mortality. As oestrogen is a potential vasodilator of the pulmonary circulation, this study examined the mechanisms by which 17 beta-oestradiol improves monocrotaline (MCT)-induced pulmonary hypertension. Female Sprague-Dawley rats underwent bilateral ovariectomy or sham operations. The rats received MCI (50 mg.kg(-1)) and were treated with 17 beta-oestradiol (1 mg.kg(-1) per day) for either 5 weeks or only from week 4 to week 5. Plasma 17 beta-oestradiol concentrations were decreased in sham-operated, MCT-treated rats when compared with sham-operated rats (17.7 +/- 4.7 versus 50.3 +/- 15.4 pg.mL(-1); p=0.029). The 17 beta-oestradiol anabolic enzyme cytochrome P450 (CYP)-19 was decreased by MCT treatment, while the catabolic enzymes CYP-1A1 and -1B1 were increased. Ovariectomised and MCI-treated rats had more severe pulmonary hypertension. 17 beta-oestradiol suppressed pulmonary arterial smooth muscle cell proliferation and macrophage infiltration, and enhanced apoptosis by increasing nitric oxide (NO) and prostacyclin (prostaglandin (PG)I-2) levels and reducing endothelin (ET)-1 levels. Phosphoinositide-3-kinase (PI3K) and Akt phosphorylations were markedly increased, but were inhibited by 17 beta-oestradiol treatment in rats with pulmonary hypertension. Oestrogen deficiency may aggravate development of pulmonary hypertension. 17 beta-oestradiol improved pulmonary hypertension via activation of the PI3K/Akt pathway to regulate NO, PGI(2) and ET-1 expression. |
| URI | http://hdl.handle.net/20.500.11897/401250 |
| ISSN | 0903-1936 |
| DOI | 10.1183/09031936.00044112 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
