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Diabetologia
Published in: Diabetologia 2/2004

01-02-2004 | Article

ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes

Authors: Dr. M.-L. Groß, N. Heiß, M. Weckbach, A. Hansen, A. El-Shakmak, A. Szabo, K. Münter, E. Ritz, K. Amann

Published in: Diabetologia | Issue 2/2004

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Abstract

Aims/hypothesis

There is little information whether cardiac capillary supply is deranged in diabetes. Hyperglycaemia is a potent stimulus for endothelin-1 (ET-1) production. We therefore hypothesised that increased ET-1 production in Streptozotocin-induced Type 1 diabetes causes abnormalities of cardiac capillaries and the aorta. To this end we compared the effects of an ET receptor A blocker (ETA-RB) with that of an ACE-inhibitor (ACE-i) or their combination in rats with Streptozotocin (STZ) diabetes.

Methods

Sprague Dawley rats were injected with 65 mg STZ i.v. and subsequently developed diabetes. Rats were left untreated or received daily either the ACE-i Trandolapril, the ETA-RB Darusentan or a combination of both. After 6 months the experiment was terminated and the heart and the aorta were investigated using quantitative morphological techniques.

Results

ACE-i but not ETA-RB lowered blood pressure in STZ Type 1 diabetic rats. Capillary length density was lower in untreated STZ diabetic rats (2932±128 mm/mm3) compared to non-diabetic control rats (3410±252 mm/mm3). Treatment with ACE-i (3568±431 mm/mm3), but not with ETA-RB (2893±192 mm/mm3), prevented the decrease in capillary supply. Volume density of the myocardial interstitium was higher in untreated STZ diabetic rats (0.86±0.04%) compared to non-diabetic control rats (0.36±0.06%). In all three intervention groups the values were lower (ACE-i: 0.53±0.05%, ETA-RB: 0.7±0.08% and combination: 0.69±0.1).

Conclusion/interpretation

Our study identifies a capillary defect of the heart in STZ diabetes, i.e. decreased capillary supply. This abnormality was reversed by ACE-i, but not by ETA-R blockade. A similar trend, although not complete normalisation, was seen in cardiac fibrosis.
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Metadata
Title
ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes
Authors
Dr. M.-L. Groß
N. Heiß
M. Weckbach
A. Hansen
A. El-Shakmak
A. Szabo
K. Münter
E. Ritz
K. Amann
Publication date
01-02-2004
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 2/2004
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-003-1309-z

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