Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension.
Cardiac fibrosis is one of the deleterious events accompanying hypertension that may be implicated in the progression toward heart failure. To determine the mechanisms involved in fibrosis and the role of hemodynamic versus humoral factors, we studied the expression of genes involved in hypertrophy and fibrosis in the heart of rats treated with aldosterone for 2 months with addition of 1% NaCl and 0.3% KCl in water. This treatment induced arterial hypertension, a moderate left ventricular hypertrophy, and a decrease in plasma thyroxine. Equatorial sections of hearts from treated rats showed numerous foci of proliferating nonmuscular cells and a biventricular fibrosis. Computerized videodensitometry demonstrated an increase of collagen volume fraction by 152% and 146% and of the ratio of the perivascular collagen area and vascular area by 86% and 167% in left and right ventricles, respectively. As measured by slot blot, this cardiac fibrosis was accompanied by an increase in alpha 1-I procollagen mRNA by 75% and 160% (P < .01) and in alpha 1-III mRNA by 76% and 319% (P < .01) in left and right ventricles, respectively. Atrial natriuretic peptide mRNA was induced only in the hypertrophied left ventricle. We conclude that fibrosis is occurring and involves pretranslational regulation of collagen synthesis. Whereas hypertrophy and atrial natriuretic peptide mRNA increase are restricted to the left ventricle, fibrosis is initiated in both ventricles, supporting the hypothesis that this cardiac response is independent of hemodynamic factors.
Robert
V
V
INSERM U127, Hôpital Lariboisière, Paris, France.
Van Thiem
N
N
Cheav
S L
SL
Mouas
C
C
Swynghedauw
B
B
Delcayre
C
C
D000450:Aldosterone / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000235:genetics*; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000008:administration & dosage*
D012333:RNA, Messenger; D012965:Sodium Chloride; D000450:Aldosterone; D003094:Collagen