Premium
Metformin Improves Endothelial Function in Obese Rats
Author(s) -
Lobato Nubia Souza,
Akamine Eliana Hiromi,
Filgueira Fernando Paranaiba,
Tostes Rita de Cássia,
Carvalho Maria Helena Catelli,
Fortes Zuleica Bruno
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.578.1
Subject(s) - medicine , endocrinology , monosodium glutamate , insulin resistance , nitric oxide , vasodilation , endothelial dysfunction , metformin , sodium nitroprusside , insulin , papaverine
Aim Obesity is associated with insulin resistance and vascular alterations. Since metformin (MET) improves insulin sensitivity and vascular dysfunction in diabetes, we evaluated the effects of MET on vascular reactivity in monosodium glutamate (MSG) obese rats. Methods and Results Wistar rats received MSG from day 2 to day 6 after birth for obesity induction. MSG rats (18 weeks) presented higher Lee index, fat accumulation, dyslipidemia and insulin resistance. MET (300mg/kg/day, 15 days) had beneficial effects on these parameters. In the mesenteric arteriolar bed the response to norepinephrine, enhanced in MSG rats, was corrected by MET. This correction was reverted by L‐NAME and tetraethylammonium (TEA), but not by indomethacin. The response to acetylcholine (ACh), reduced in MSG rats, was corrected by MET. L‐NAME, indomethacin or TEA did not alter this correction. The vasodilation to sodium nitroprusside was enhanced by MET. Althought MET did not alter the reduced nitric oxide (NO) production, it reverted the reduced PGI2/TXA2 release and the enhanced reactive oxygen species (ROS) generation in MSG rats. Conclusion MET restores vascular dysfunction in MSG rats by reducing ROS generation, modulating membrane hyperpolarizating and reestablishing the balanced release of prostanoids. The hyperresponsiveness of the smooth muscle to NO with MET treatment might contribute to its beneficial effects. FAPESP