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.
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 diabeticrats. Capillary length density was lower in untreated STZdiabeticrats (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 STZdiabeticrats (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 STZdiabetes, 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.
Authors: E Riva; G Andreoni; R Bianchi; R Latini; G Luvarà; G Jeremic; C Traquandi; L Tuccinardi Journal: Pharmacol Res Date: 1998-03 Impact factor: 7.658