INCREASED CARDIAC TYPE-I AND TYPE-III COLLAGEN MESSENGER-RNAS IN ALDOSTERONE-SALT HYPERTENSION

Cardiac fibrosis is one of the deleterious events accompanying hyperte nsion that may be implicated in the progression toward heart failure. To determine the mechanisms involved in fibrosis and the role of hemod ynamic versus humoral factors, we studied the expression of genes invo lved in hypertrophy and fibrosis in the heart of rats treated with ald osterone for 2 months with addition of 1% NaCl and 0.3% KCl in water. This treatment induced arterial hypertension, a moderate left ventricu lar hypertrophy, and a decrease in plasma thyroxine. Equatorial sectio ns of hearts from treated rats showed numerous foci of proliferating n onmuscular cells and a biventricular fibrosis. Computerized videodensi tometry demonstrated an increase of collagen volume fraction by 152% a nd 146% and of the ratio of the perivascular collagen area and vascula r area by 86% and 167% in left and right ventricles, respectively. As measured by slot blot, this cardiac fibrosis was accompanied by an inc rease in alpha(1)-I procollagen mRNA by 75% and 160% (P<.01) and in al pha(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 a nd involves pretranslational regulation of collagen synthesis. Whereas hypertrophy and atrial natriuretic peptide mRNA increase are restrict ed to the left ventricle, fibrosis is initiated in both ventricles, su pporting the hypothesis that this cardiac response is independent of h emodynamic factors.