Experimental cardiac fibrosis: differential time course of responses to mineralocorticoid-salt administration.
The rapid (1-4 h) responses of epithelial target tissues to mineralocorticoids contrast with the days/weeks apparently required for responses in the cardiovascular system. The present study explores the time course and pattern of early events leading to cardiac fibrosis in the mineralocorticoid-salt rat model. Uninephrectomized rats were given deoxycorticosterone (20 mg, sc, weekly) plus 0.9% NaCl/0.3% KCl to drink and were killed at 2, 4, 8, 16, and 32 d. Type III collagen increased progressively from d 2, and blood pressure from d 4, with 4 and 8 d rats showing marked perivascular inflammatory cell infiltration. Apoptosis was also noted in perivascular areas at 4 and 8 d and in scar areas at 8, 16, and 32 d. Elevation of mineralocorticoid hormone levels inappropriate for salt status thus provokes a series of changes in cardiac vessels and myocytes leading to increased collagen deposition. When mineralocorticoid levels are elevated acutely by bolus injection, changes are discernible after 2 d, in contrast with previous infusion studies in which 3-4 wk were required for measurable changes.
Fujisawa
G
G
Baker Medical Research Institute, Melbourne, Victoria 8008, Australia.
Dilley
R
R
Fullerton
M J
MJ
Funder
J W
JW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology*; D013997:Time Factors
D003900:Desoxycorticosterone; D012965:Sodium Chloride; D003094:Collagen