Effects of 17 β-estradiol and 2-methoxyestradiol on Endothelin-1/Nitric Oxide Cascade in Experimental Rats With Hypoxic Pulmonary Hypertension
10.3969/j.issn.1000-3614.2016.05.017
- VernacularTitle:17β-雌二醇和2-甲氧基雌二醇对慢性低氧性肺动脉高压大鼠体内内皮素-1/一氧化氮体系的影响
- Author:
Li WANG
;
Pei WANG
;
Yanpeng LI
;
Yadong YUAN
- Publication Type:Journal Article
- Keywords:
Hypertension,pulmonary;
Nitric oxide;
17 Beta-estradiol;
2-methoxyestradiol;
Endothelin-1
- From:
Chinese Circulation Journal
2016;31(5):489-494
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the effects of 17 β-estradiol (E2) and 2-methoxyestradiol (2ME) on endothelium-1/nitric oxide (ET-1/NO) cascade in experimental rats with hypoxic pulmonary hypertension. Methods: A total of 48 female SD rats were randomly divided into 6 groups:①Sham operation group,②Ovariectomy (OVX) group,③Hypoxia group,④OVX+hypoxia group,⑤OVX+hypoxia+E2 group, the rats received subcutaneous E2 at 20μg/(kg?d) and⑥OVX+hypoxia+2ME group, the rats received subcutaneous 2ME at 240μg/(kg?d).n=8 in each group. Blood levels of ET-1, NO, eNOS activity and the expressions of pulmonary tissue endothelium A receptor (ETAR), ETBR and eNOS were compared among different groups. Results: Compared with Sham operation group, Hypoxia and OVX+hypoxia groups showed small pulmonary artery thickening with lumen narrowing, increased mean pulmonary arterial pressure (mPAP), allP<0.01; the above morphological and mPAP changes were reduced by E2 and 2ME intervention. Compared with Sham operation group, OVX and Hypoxia groups had increased blood ET-1 and pulmonary mRNA, protein expressions of ETAR, decreased pulmonary ETBR, all P<0.01; the above changes were more obvious in OVX+hypoxia group; E2 and 2ME intervention reduced blood ET-1 and pulmonary ETAR expression, but they were still higher than Sham operation group, meanwhile, ETBR expression was elevated, but it was still lower than Sham operation group, allP<0.01; blood ET-1 was lower in OVX+hypoxia+2ME group than OVX+hypoxia+E2 group,P<0.05. Compared with Sham operation group, OVX group had decreased pulmonary eNOS protein expression,P<0.01; Hypoxia group had decreased blood NO and pulmonary eNOS protein expression,P<0.05 orP<0.01; OVX+hypoxia group had decreased blood NO, eNOS activity and decreased pulmonary mRNA and protein expressions of eNOS, allP<0.01; E2 and 2ME intervention elevated the above indexes,P<0.05 orP<0.01, but they were still lower than Sham operation group, allP<0.05. Conclusion: E2 and 2ME could decrease blood ET-1 and pulmonary ETAR expression, increase pulmonary ETBR expression; elevate blood NO, eNOS activity and pulmonary eNOS expression. E2 and 2ME may partially reverse pulmonary hypertension via improving ET-1/NO cascade in experimental rats.
