(Hypertension. 1995;26:971-978.)
© 1995 American Heart Association, Inc.
Articles |
Biological Determinants of Aldosterone-Induced Cardiac Fibrosis in Rats
From INSERM U127, and Service d'Anatomo-Pathologie (M.W.), Hôpital Lariboisière, IFR "Circulation," Université Denis Diderot, Paris, France.
Abstract To determine the events leading to cardiac
fibrosis in aldosterone-salt hypertensive rats, we
studied protein and mRNA accumulation of procollagens I and III for 60
days. After 3 and 7 days of treatment systolic pressure was
normal, and no histological or biochemical changes were
seen in rat hearts. At day 15 arterial pressure was raised
(+40%) and left ventricular hypertrophy was
+15%. Cardiac examination after hemalun-eosin staining and
immunolabeling with anticollagen I and III antibodies showed no
structural alterations, but an 83% increase in right
ventricular type III procollagen mRNA levels was found. At
30 and 60 days we found progressive cardiac fibrosis, with inflammatory
cells, myocyte necrosis, and elevation of both types I and III
procollagen mRNA levels in both ventricles. To determine whether
aldosterone had effects on Na,K-ATPase that might lead to
ionic disturbances and induce myocyte necrosis, we studied the
major cardiac Na,K-ATPase isoform genes. Although Na,K-ATPase
1- and ß1-subunit mRNA levels were
elevated in kidney at day 1, neither of these cardiac transcripts nor
the specific 2 isoform was altered between 1 and 15
days. These results show that accumulation of procollagen mRNAs occurs
before collagen deposition. Cardiac alterations are late and not
preceded by changes in Na,K-ATPase cardiac gene expression, precluding
a direct modulation of cardiac collagen synthesis and Na,K-ATPase by
aldosterone.
Key Words: aldosterone • collagen • fibrosis • Na+,K+-transporting ATPase • heart
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