MINERALOCORTICOIDS, HYPERTENSION, AND CARDIAC FIBROSIS

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.