The renin-angiotensin-aldosterone system in experimental
mineralocorticoid-salt induced cardiac fibrosis.
Young, Morag J., and John W. Funder.
Baker Medical Research Institute, Melbourne, Australia
APStracts 3:0157E, 1996.
Aldosterone infused for eight weeks to uninephrectomized rats drinking
saline solution causes cardiac fibrosis. To investigate the renin
-angiotensin system (RAS) in this process, we have blocked ACE with
Perindopril and AT-1 receptors with Losartan. To distinguish
aldosterone effects via 11[beta] hydroxysteroid dehydrogenase-2
protected, epithelial mineralocorticoid receptors (MR) and
unprotected cardiac MR, we have compared preferential exclusion of
aldosterone from unprotected MR by corticosterone and generalised MR
blockade by potassium canrenoate. Perindopril and Losartan modestly
lowered BP; neither affected cardiac hypertrophy, hydroxyproline
content, or perivascular fibrosis; both slightly attenuated
aldosterone effects on interstitial collagen. Corticosterone did not
affect cardiac hypertrophy, but halved aldosterone-induced elevation
of BP and collagen levels; canrenoate halved the increase in BP and
hypertrophy, and completely reversed aldosterone-induced increase in
cardiac collagen. We conclude that 1) the circulating and tissue RAS
are at most minor contributors to cardiac fibrosis in aldosterone
-infused, salt-loaded rats; and 2) both BP elevation and increased
cardiac collagen appear to reflect aldosterone occupancy of
unprotected MR, consistent with a direct cardiac effect of
aldosterone on fibrosis.
Received 5 February 1996; accepted in final form 28 June 1996.
APS Manuscript Number E65-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996