Uninephrectomized rats drinking 1% sodium chloride were given aldoster
one (Aldo, 0.75 mu g/h, subcutaneous [s.c.] infusion), deoxycorticoste
rone( DOC, 20 mg/wk, s.c.), corticosterone (B, 2 mg/d, s.c.), or the a
ntiglucocorticoid-antiprogestin RU486 (2 mg/d, s.c.) for 8 wk, and hem
odynamic and tissue responses were compared with a non-steroid-treated
control group. Aldo and DOC markedly increased systolic BP and caused
considerable (40-50%) cardiac hypertrophy; B and RU386 caused neither
hypertension nor cardiac hypertrophy. Measurements of ventricular cro
ss-sectional areas shelved hypertrophy due to an increase in mass of t
he left ventricle only. Cardiac hydroxyproline concentration was incre
ased considerably by Aldo and DOC to a lesser degree by RU386, and not
by B. Aldo markedly elevated left ventricular interstitial collagen (
2.5-fold, vs control, P < 0.01 vs all groups); other steroid treatment
s also increased interstitial collagen over control (DOC x 1.8-, RU386
x 1.6-, B x 13-fold), with identical responses for right and left ven
tricles (r = 0.91). A different pattern of perivascular fibrosis was n
oted; DOC elevated perivascular collagen (2.1-fold vs control, P < 0.0
1, vs all other groups); RU486 raised levels 1.4-fold vs control, but
neither Aldo nor B significantly affected perivascular collagen. These
data are consistent with interstitial cardiac fibrosis reflecting typ
e I (mineralocorticoid) receptor occupancy by administered Aldo or DOC
, or by elevated endogenous B after type II (glucocorticold) receptor
blockade after RU386 administration; perivascular fibrosis may reflect
a composite response after type I receptor agonist/type II glucocorti
coid receptor antagonist occupancy.