title: Improvement of metabolic parameters and vascular function by metformin in obese non-diabetic rats.
abstract: OBJECTIVE
  Metformin is an insulin sensitizing agent with beneficial effects in diabetic patients on glycemic levels and in the cardiovascular system. We examined whether the metabolic changes and the vascular dysfunction in monosodium glutamate-induced obese non-diabetic (MSG) rats might be improved by metformin.
  
  
  METHODS
  16 week-old MSG rats were treated with metformin for 15 days and compared with age-matched untreated MSG and non-obese non-diabetic rats (control). Blood pressure, insulin sensitivity, vascular reactivity and prostanoid release in the perfused mesenteric arteriolar bed as well as nitric oxide production and reactive oxygen species generation in isolated mesenteric arteries were analyzed.
  
  
  RESULTS
  18-week-old MSG rats displayed higher Lee index, fat accumulation, dyslipidemia, insulin resistance and hyperinsulinemia. Metformin treatment improved these alterations. The norepinephrine-induced response, increased in the mesenteric arteriolar bed from MSG rats, was corrected by metformin. Indomethacin corrected the enhanced contractile response in MSG rats but did not affect metformin effects. The sensitivity to acetylcholine, reduced in MSG rats, was also corrected by metformin. Indomethacin corrected the reduced sensitivity to acetylcholine in MSG rats but did not affect metformin effects. The sensitivity to sodium nitroprusside was increased in preparations from metformin-treated rats. Metformin treatment restored both the reduced PGI2/TXA2 ratio and the increased reactive oxygen species generation in preparations from MSG rats.
  
  
  CONCLUSIONS
  Metformin improved the vascular function in MSG rats through reduction in reactive oxygen species generation, modulation of membrane hyperpolarization, correction of the unbalanced prostanoids release and increase in the sensitivity of the smooth muscle to nitric oxide.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: N S
authors.initials: NS
authors.lastname: Lobato
authors.forename: F P
authors.initials: FP
authors.lastname: Filgueira
authors.forename: G N
authors.initials: GN
authors.lastname: Hagihara
authors.forename: E H
authors.initials: EH
authors.lastname: Akamine
authors.forename: J R
authors.initials: JR
authors.lastname: Pariz
authors.forename: R C
authors.initials: RC
authors.lastname: Tostes
authors.forename: M H C
authors.initials: MH
authors.lastname: Carvalho
authors.forename: Z B
authors.initials: ZB
authors.lastname: Fortes
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000188:drug therapy; D011464:Epoprostenol / Q000378:metabolism; D006946:Hyperinsulinism / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D008687:Metformin / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012970:Sodium Glutamate / Q000008:administration & dosage; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D017382:Reactive Oxygen Species; D009599:Nitroprusside; D009569:Nitric Oxide; D013928:Thromboxane A2; D008687:Metformin; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D012970:Sodium Glutamate; D009638:Norepinephrine; D007213:Indomethacin