Obesity induced by neonatal treatment with monosodium glutamate impairs microvascular reactivity in adult rats: Role of NO and prostanoids

Lobato, N.S.; Filgueira, F.P.; Akamine, E.H.; Davel, A.P.C.; Rossoni, L.V.; Tostes, R.C.; Carvalho, M.H.C.; Fortes, Z.B.

doi:10.1016/j.numecd.2010.02.006

« Previous Next »Nutrition, Metabolism & Cardiovascular Diseases
Volume 21, Issue 10 , Pages 808-816, October 2011

Obesity induced by neonatal treatment with monosodium glutamate impairs microvascular reactivity in adult rats: Role of NO and prostanoids

N.S. Lobato
- Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil
F.P. Filgueira
- Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil
E.H. Akamine
- Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil
A.P.C. Davel
- Department of Physiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
L.V. Rossoni
- Department of Physiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
R.C. Tostes
- Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil
M.H.C. Carvalho
- Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil
Z.B. Fortes
- Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil
- Corresponding author. Tel./fax: +55 11 3091 7317.

Received 3 August 2009; received in revised form 5 February 2010; accepted 8 February 2010. published online 31 May 2010.

Abstract

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

Keywords: Obesity, Monosodium glutamate, Mesenteric arteriolar bed, Nitric oxide, Prostanoids, Reactive oxygen species