Obesity induced by neonatal treatment with monosodium glutamate impairs microvascular reactivity in adult rats: Role of NO and prostanoids
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2011
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Resumo |
Background and aim: given that obesity is an independent risk factor for the development of cardiovascular diseases we decided to investigate the mechanisms involved in microvascular dysfunction using a monosodium glutamate (MSG)-induced model of obesity, which allows us to work on both normotensive and normoglycemic conditions. Methods and results: Male offspring of Wistar rats received MSG from the second to the sixth day after birth. Sixteen-week-old MSG rats displayed higher Lee index, fat accumulation, dyslipidemia and insulin resistance, with no alteration in glycemia and blood pressure. The effect of norepinephrine (NE), which was increased in MSG rats, was potentiated by L-nitro arginine methyl ester (L-NAME) or tetraethylammonium (TEA) and was reversed by indomethacin and NS-398. Sensitivity to acetylcholine (ACh), which was reduced in MSG rats, was further impaired by L-NAME or TEA, and was corrected by indomethacin, NS-398 and tetrahydrobiopterin (BH4). MSG rats displayed increased endothelium-independent relaxation to sodium nitroprusside. A reduced prostacyclin/tromboxane ratio was found in the mesenteric beds of MSG rats. Mesenteric arterioles of MSG rats also displayed reduced nitric oxide (NO) production along with increased reactive oxygen species (ROS) generation; these were corrected by BH4 and either L-NAME or superoxide dismutase, respectively. The protein expression of eNOS and cyclooxygenase (COX)-2 was increased in mesenteric arterioles from MSG rats. Conclusion: Obesity/insulin resistance has a detrimental impact on vascular function. Reduced NO bioavailability and increased ROS generation from uncoupled eNOS and imbalanced release of COX products from COX-2 play a critical role in the development of these vascular alterations (C) 2010 Elsevier B.V. All rights reserved. Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Programa de Apoio a Nucleos de Excelencia (PRONEX), Brazil Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) |
Identificador |
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, v.21, n.10, p.808-816, 2011 0939-4753 http://producao.usp.br/handle/BDPI/28150 10.1016/j.numecd.2010.02.006 |
Idioma(s) |
eng |
Publicador |
ELSEVIER SCI LTD |
Relação |
Nutrition Metabolism and Cardiovascular Diseases |
Direitos |
restrictedAccess Copyright ELSEVIER SCI LTD |
Palavras-Chave | #Obesity #Monosodium glutamate #Mesenteric arteriolar bed #Nitric oxide #Prostanoids #Reactive oxygen species #SPONTANEOUSLY HYPERTENSIVE RATS #NITRIC-OXIDE #ENDOTHELIAL DYSFUNCTION #HYPOTHALAMIC OBESITY #INSULIN-RESISTANCE #DIABETES-MELLITUS #ANGIOTENSIN-II #ZUCKER RATS #FEMALE RATS #IN-VIVO #Cardiac & Cardiovascular Systems #Endocrinology & Metabolism #Nutrition & Dietetics |
Tipo |
article original article publishedVersion |