Aortic cell apoptosis in rat primary aldosteronism model.
This study aimed to determine whether aldosterone could induce vascular cell apoptosis in vivo. Thirty-two male rats were randomly divided into 4 groups: vehicle (control), aldosterone, aldosterone plus eplerenone or hydralazine. They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method. After 8 weeks, plasma aldosterone concentration (PAC) and renin activity (PRA) were determined by radioimmunoassay. Aortic apoptosis was examined by TUNEL assay. The levels of cytochrome c and caspase-3 were determined by Western blotting and the expression of Bax and Bcl-2 was detected by immunohistochemistry and Western blotting. The results showed that as compared with control group, aldosterone-infused rats exhibited: (1) an increase in SBP; (2) significantly elevated PAC with depressed PRA; (3) elevated aortic vascular cell apoptosis accompanied with higher levels of cytochrome c and activated caspase-3; and (4) significantly up-regulated Bax protein with down-regulated Bcl-2. These effects of aldosterone were significantly inhibited after co-administration with eplerenone but not with hydralazine. It was concluded that aldosterone induced vascular cell apoptosis by its direct effect on the aorta via mineralocorticoid receptors and independently of blood pressure, which may contribute to aldosterone-mediated vascular injury.
Yan
Yongji
Y
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 7577yyj@163.com
Ouyang
Jinzhi
J
Wang
Chao
C
Wu
Zhun
Z
Ma
Xin
X
Li
Hongzhao
H
Xu
Hua
H
Hu
Zheng
Z
Li
Jun
J
Wang
Baojun
B
Shi
Taoping
T
Gong
Daojing
D
Ni
Dong
D
Zhang
Xu
X
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001011:Aorta / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology*; D042783:Endothelial Cells / Q000473:pathology*; D006929:Hyperaldosteronism / Q000473:pathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone