title: Blockade of the renin-angiotensin system improves cerebral microcirculatory perfusion in diabetic hypertensive rats.
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 AT1-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.
authors: Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, RJ, Brazil. Electronic address: estato@ioc.fiocruz.br.
authors: Vanessa
authors: V
authors: Estato
authors: Nathalie
authors: N
authors: Obadia
authors: Juliana
authors: J
authors: Carvalho-Tavares
authors: Felipe Santos
authors: FS
authors: Freitas
authors: Patrícia
authors: P
authors: Reis
authors: Hugo
authors: H
authors: Castro-Faria Neto
authors: Marcos Adriano
authors: MA
authors: Lessa
authors: Eduardo
authors: E
authors: Tibiriçá
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat; D004656:Enalapril / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D036904:Leukocyte Rolling / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013311:Streptozocin; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D013777:Tetrazoles; D013311:Streptozocin; D004656:Enalapril; C437965:olmesartan