Article date: July 1997
By: C Grohé, S Kahlert, K Löbbert, M Eickels, M Stimpel, H Vetter, L Neyses, in Volume 121, Issue 7, pages 1350-1354
The effects of 2‐2‐(1‐(ethoxycarbonyl)‐3‐phenylpropyl)‐[amino‐oxopropyl]−6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐3 carboxylic acid (moexiprilat), 17β‐oestradiol (E2), oestrone (ES) and angiotensin II (AII) on growth and activation of oestrogen receptors and the immediate‐early gene egr‐1 were investigated in neonatal rat cardiac fibroblasts of female and male origin.
In BrdU proliferation assays, oestrone (10−7–10−9M) stimulated cardiac fibroblast growth in a concentration‐dependent fashion (maximum at 10−7M, 4.0 fold±0.14 in female and 3.1 fold±0.06 in male cells, n=9, P<0.05), while E2 (10−7–10−9M) had no effect. Moexiprilat (10−7M) completely inhibited oestrone‐induced cardiac fibroblast growth.
Angiotensin II (10−7M) induced cardiac fibroblast growth (female 4.1 fold±0.1/male 3.9 fold±0.2; n=9, P<0.05). Angiotensin II induced oestrogen receptor (maximum 21.8 fold at 60 min) and egr‐1 (maximum 47.5 fold at 60 min) expression in a time‐dependent fashion.
In immunoblot experiments, oestrogen activated oestrogen receptor (ES: 12.8 fold±2.0; E2: 14.7 fold±4.9; n=3, P<0.05) and egr‐1 (ES: 5.1 fold,±0.24; E2: 3.8 fold,±0.25; n=3, P<0.05) expression. The induction of oestrogen receptor and egr‐1 protein expression was time‐dependent and inhibited by moexiprilat.
Our results show that oestrone and 17β‐oestradiol reveal a significant difference in their potential to activate cardiac fibroblast growth in female and male cells and that oestrone‐stimulated growth is inhibited by moexiprilat. The inhibition of oestrone‐stimulated cardiac fibroblast growth by moexiprilat may contribute to the beneficial effects seen in postmenopausal women with hypertensive heart disease treated with ACE inhibitors.
The effects of 2‐2‐(1‐(ethoxycarbonyl)‐3‐phenylpropyl)‐[amino‐oxopropyl]−6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐3 carboxylic acid (moexiprilat), 17β‐oestradiol (E2), oestrone (ES) and angiotensin II (AII) on growth and activation of oestrogen receptors and the immediate‐early gene egr‐1 were investigated in neonatal rat cardiac fibroblasts of female and male origin.
In BrdU proliferation assays, oestrone (10−7–10−9M) stimulated cardiac fibroblast growth in a concentration‐dependent fashion (maximum at 10−7M, 4.0 fold±0.14 in female and 3.1 fold±0.06 in male cells, n=9, P<0.05), while E2 (10−7–10−9M) had no effect. Moexiprilat (10−7M) completely inhibited oestrone‐induced cardiac fibroblast growth.
Angiotensin II (10−7M) induced cardiac fibroblast growth (female 4.1 fold±0.1/male 3.9 fold±0.2; n=9, P<0.05). Angiotensin II induced oestrogen receptor (maximum 21.8 fold at 60 min) and egr‐1 (maximum 47.5 fold at 60 min) expression in a time‐dependent fashion.
In immunoblot experiments, oestrogen activated oestrogen receptor (ES: 12.8 fold±2.0; E2: 14.7 fold±4.9; n=3, P<0.05) and egr‐1 (ES: 5.1 fold,±0.24; E2: 3.8 fold,±0.25; n=3, P<0.05) expression. The induction of oestrogen receptor and egr‐1 protein expression was time‐dependent and inhibited by moexiprilat.
Our results show that oestrone and 17β‐oestradiol reveal a significant difference in their potential to activate cardiac fibroblast growth in female and male cells and that oestrone‐stimulated growth is inhibited by moexiprilat. The inhibition of oestrone‐stimulated cardiac fibroblast growth by moexiprilat may contribute to the beneficial effects seen in postmenopausal women with hypertensive heart disease treated with ACE inhibitors.
DOI: 10.1038/sj.bjp.0701263
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