Determinants of cardiac fibrosis in experimental hypermineralocorticoid states. Young, Morag, Geoff Head, and John Funder. Baker Medical Research Institute, P.O. Box 348, Prahran, 3181 Victoria, Australia
APStracts 2:0105E, 1995.
Uninephrectomized rats maintained on 1.0% NaCl to drink and infused with aldosterone (0.75[mu]g/hr) for 8 weeks have previously been shown to develop hypertension, cardiac hypertrophy and cardiac fibrosis. In the present study we have shown that potassium supplementation (1.0% NaCl plus 0.4% KCl drinking solution) alters neither the interstitial nor the perivascular fibrotic response to mineralocorticoid treatment. Secondly, rats receiving 0.75[mu]g/hr 9[alpha]-fluorocortisol, a mineralocorticoid and glucocorticoid agonist, respond with hypertension and cardiac fibrosis without cardiac hypertrophy. Finally, intracerebroventricular infusion of the mineralocorticoid receptor antagonist RU28318 blocks blood pressure elevation, but not cardiac hypertrophy or fibrosis, when aldosterone is co-infused peripherally. We conclude that the myocardial fibrosis observed in response to chronic mineralocorticoid elevation and salt loading is a humorally-mediated event independent of hypokalemia, hypertension and cardiac hypertrophy. It remains to be determined whether the fibrosis observed in the presence of excess salt represents a direct (e.g. cardiac) effect of mineralocorticoid hormones, or one mediated via a primary action on classical epithelial aldosterone target tissues (e.g. kidney). 

Received 7 February 1995; accepted in final form 10 May 1995.
APS Manuscript Number E54-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.