Abstract 433: Plasma and Urinary Aldosterone Levels in Rats with Non-Insulin Dependent Diabetes Mellitus - Association with Myocardial Fibrosis
Initial stages of diabetic cardiomyopathy in hyperinsulinemic rats are characterized by cardiomyocyte hypertrophy, enhanced cardiac contractility and marked perivascular fibrosis. Aldosterone is known to be an important component of the neurohumoral system playing a pivotal role in the development of cardiac fibrosis. It is therefore hypothesized that aldosterone is involved in morphological changes of the heart seen in type 2 diabetes which may be modified by treatment with an ACE inhibitor (ACE-I). Zucker Diabetic Fatty rats aged 13 weeks were treated with ACE-I (Ramipril 1 mg/kg/d, ZDF+ACE-I, n=7) or placebo (ZDF, n=8) äover 11 weeks. Heterozygous rats served as non-diabetic controls (Ctr, n=8). Plasma (AldoP), urinary aldosterone from week 23 (AldoU) and plasma renin activity were measured by RIA. Myocardial perivascular fibrosis (PVF) was assessed by immunohistology of collagen I and quantified by image analysis.
Results: Values are given as mean±SEM (see table⇓). In contrast to renin activity, plasma and urinary aldosterone levels were significantly increased in diabetic animals. AldoS correlated positively with myocardial PVF (r=0.64, p<0.05). Serial measurement of AldoU showed that AldoU was already significantly elevated in all diabetic groups at the beginning of diabetes and that normalization under treatment was reached at the earliest 7 weeks after initiation of ACE-I. In conclusion, experimental diabetes is associated with a hyporeninemic hyperaldosteronism, Further, the experiments suggest an association between myocardial fibrosis and chronic inappropriate elevations in circulating aldosterone in type 2 diabetes despite low renin activity. Early treatment with ACE-I alone may not be sufficient to prevent cardiac remodelling in diabetic ZDF rats - especially as Aldo levels rise early in diabetes and last for some time after initiation of ACE-I .