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 17β-oestradiol improves monocrotaline (MCT)-induced pulmonary hypertension.
Female Sprague–Dawley rats underwent bilateral ovariectomy or sham operations. The rats received MCT (50 mg·kg−1) and were treated with 17β-oestradiol (1 mg·kg−1 per day) for either 5 weeks or only from week 4 to week 5. Plasma 17β-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 17β-oestradiol anabolic enzyme cytochrome P450 (CYP)-19 was decreased by MCT treatment, while the catabolic enzymes CYP-1A1 and -1B1 were increased. Ovariectomised and MCT-treated rats had more severe pulmonary hypertension. 17β-oestradiol suppressed pulmonary arterial smooth muscle cell proliferation and macrophage infiltration, and enhanced apoptosis by increasing nitric oxide (NO) and prostacyclin (prostaglandin (PG)I2) levels and reducing endothelin (ET)-1 levels. Phosphoinositide-3-kinase (PI3K) and Akt phosphorylations were markedly increased, but were inhibited by 17β-oestradiol treatment in rats with pulmonary hypertension.
Oestrogen deficiency may aggravate development of pulmonary hypertension. 17β-oestradiol improved pulmonary hypertension via activation of the PI3K/Akt pathway to regulate NO, PGI2 and ET-1 expression.
Footnotes
For editorial comments see page 1014.
Support Statement
This work was supported by the Innovation Programme of Shanghai Municipal Education Commission (09ZZ35), Programme of National Natural Science Foundation of China (81170300), Programme for Shanghai Outstanding Academic Leader, the “Dawn” Programme of the Shanghai Education Commission (10SG25), Programme for New Century Excellent Talents in University (NCET-10-0630), and The New and Frontier Project of Shanghai Shenkang Hospital Development Centre (SHDC12010102).
Statement of Interest
Conflict of interest information can be found alongside the online version of this article at www.ersjournals.com
- Received March 13, 2012.
- Accepted August 3, 2012.
- ©ERS 2013