Mineralocorticoids, hypertension, and cardiac fibrosis.
Uninephrectomized rats drinking 1% sodium chloride were given aldosterone (Aldo, 0.75 microgram/h, subcutaneous [s.c.] infusion), deoxycorticosterone (DOC, 20 mg/wk, s.c.), corticosterone (B, 2 mg/d, s.c.), or the antiglucocorticoid-antiprogestin RU486 (2 mg/d, s.c.) for 8 wk, and hemodynamic 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 RU486 caused neither hypertension nor cardiac hypertrophy. Measurements of ventricular cross-sectional areas showed hypertrophy due to an increase in mass of the left ventricle only. Cardiac hydroxyproline concentration was increased considerably by Aldo and DOC, to a lesser degree by RU486, and not by B. Aldo markedly elevated left ventricular interstitial collagen (2.5-fold vs control, P < 0.01 vs all groups); other steroid treatments also increased interstitial collagen over control (DOC x 1.8-, RU486 x 1.6-, B x 1.3-fold), with identical responses for right and left ventricles (r = 0.94). A different pattern of perivascular fibrosis was noted; DOC elevated perivascular collagen (2.1-fold vs control, P < 0.01 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 type I (mineralocorticoid) receptor occupancy by administered Aldo or DOC, or by elevated endogenous B after type II (glucocorticoid) receptor blockade after RU486 administration; perivascular fibrosis may reflect a composite response after type I receptor agonist/type II glucocorticoid receptor antagonist occupancy.
Young
M
M
Baker Medical Research Institute, Melbourne, Australia.
Fullerton
M
M
Dilley
R
R
Funder
J
J
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003094:Collagen / Q000032:analysis; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004719:Endomyocardial Fibrosis / Q000139:chemically induced*; D006909:Hydroxyproline / Q000032:analysis; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015735:Mifepristone; D003900:Desoxycorticosterone; D000450:Aldosterone; D003094:Collagen; D006909:Hydroxyproline