ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes
| Autor: | Alexander Hansen, Attila J. Szabo, Kerstin Amann, A. El-Shakmak, N. Heiß, Klaus Münter, M.-L. Groß, Eberhard Ritz, M. Weckbach |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Blood Glucose
Collagen Type IV Male Trandolapril medicine.medical_specialty Indoles Endothelin A Receptor Antagonists Cardiac fibrosis Endocrinology Diabetes and Metabolism Gene Expression Angiotensin-Converting Enzyme Inhibitors Aorta Thoracic Blood Pressure Diabetes Mellitus Experimental Rats Sprague-Dawley Transforming Growth Factor beta Diabetes mellitus Internal medicine Internal Medicine Albuminuria Animals Medicine In Situ Hybridization Endothelin-1 Phenylpropionates business.industry Myocardium Body Weight Heart Receptor Endothelin A medicine.disease Streptozotocin Coronary Vessels Fibrosis Immunohistochemistry Rats Arterioles Pyrimidines Endocrinology Cardiovascular Diseases ACE inhibitor Circulatory system Darusentan business Endothelin receptor medicine.drug |
| Zdroj: | Diabetologia. 47:316-324 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-003-1309-z |
| Popis: | 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.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.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).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. |
| Databáze: | OpenAIRE |
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