1 The effects of yl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3 ca
rboxylic acid (moexiprilat), 17 beta-oestradiol (E-2), oestrone (ES) a
nd angiotensin II (AII) on growth and activation of oestrogen receptor
s and the immediate-early gene egr-1 were investigated in neonatal rat
cardiac fibroblasts of female and male origin. 2 In BrdU proliferatio
n assays, oestrone (10(-7)-10(-9) M) stimulated cardiac fibroblast gro
wth in a concentration-dependent fashion (maximum at 10(-7) M, 4.0 fol
d +/- 0.14 in female and 3.1 fold +/- 0.06 in male cells, n = 9, P < 0
.05), while E-2 (10(-7)-10(-9) M) had no effect. Moexiprilat (10(-7) M
) completely inhibited oestrone-induced cardiac fibroblast growth. 3 A
ngiotensin II (10(-7) M) 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 (ma
ximum 47.5 fold at 60 min) expression in a time-dependent fashion. 4 I
n immunoblot experiments, oestrogen activated oestrogen receptor (ES:
12.8 fold +/- 2.0; E-2: 14.7 fold +/- 4.9; n = 3, P < 0.05) and egr-1
(ES: 5.1 fold, +/- 0.24; E-2: 3.8 fold, +/- 0.25; n = 3, P < 0.05) exp
ression. The induction of oestrogen receptor and egr-1 protein express
ion was time-dependent and inhibited by moexiprilat. 5 Our results sho
w that oestrone and 17 beta-oestradiol reveal a significant difference
in their potential to activate cardiac fibroblast growth in female an
d male cells and that oestrone-stimulated growth is inhibited by moexi
prilat. The inhibition of oestrone-stimulated cardiac fibroblast growt
h by moexiprilat may contribute to the beneficial effects seen in post
menopausal women with hypertensive heart disease treated with ACE inhi
bitors.