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Blockade of the renin-angiotensin system improves cerebral microcirculatory perfusion in diabetic hypertensive rats
Journal article   Open access   Peer reviewed

Blockade of the renin-angiotensin system improves cerebral microcirculatory perfusion in diabetic hypertensive rats

Vanessa Estato, Nathalie Obadia, Juliana Carvalho-Tavares, Felipe Santos Freitas, Patricia Reis, Hugo Castro-Faria Neto, Marcos Adriano Lessa and Eduardo Tibirica
Microvascular research, Vol.87, pp.41-49
05/01/2013
DOI: 10.1016/j.mvr.2013.02.007
PMID: 23466285
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https://doi.org/10.1016/j.mvr.2013.02.007View
Published (Version of record) Open Access

Abstract

We examined the functional and structural microcirculatory alterations in the brain, skeletal muscle and myocardium of non-diabetic spontaneously hypertensive rats (SHR) and diabetic SHR (D-SHR), as well as the effects of long-term treatment with the angiotensin AT(1)-receptor antagonist olmesartan and the angiotensin-converting enzyme inhibitor enalapril. Diabetes was experimentally induced by a combination of a high-fat diet with a single low dose of streptozotocin (35 mg/kg, intraperitoneal injection). D-SHR were orally administered with olmesartan (5 mg/kg/day), enalapril (10 mg/kg/day) or vehicle for 28 days, and compared with vehicle-treated non-diabetic SHR or normotensive non-diabetic Wistar Kyoto rats. The cerebral and skeletal muscle functional capillary density of pentobarbital-anesthetized rats was assessed using intravital fluorescence videomicroscopy. Chronic treatment with olmesartan or enalapril significantly lowered blood pressure and reversed brain functional capillary rarefaction. Brain oxidative stress was reduced to non-diabetic control levels in animals treated with olmesartan or enalapril. Histochemical analysis of the structural capillary density showed that both olmesartan and enalapril increased the capillary-to-fiber ratio in skeletal muscle and the capillary-to-fiber volume density in the left ventricle. Olmesartan and enalapril also prevented collagen deposition and the increase in cardiomyocyte diameter in the left ventricle. Our results suggest that the association between hypertension and diabetes results in microvascular alterations in the brain, skeletal muscle and myocardium that can be prevented by chronic blockade of the renin angiotensin system. (C) 2013 Elsevier Inc. All rights reserved.
Cardiovascular System & Cardiology Life Sciences & Biomedicine Peripheral Vascular Disease Science & Technology

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