title: Metformin ameliorates ovariectomy-induced vascular dysfunction in non-diabetic Wistar rats.
abstract: Metformin is an antihyperglycaemic drug with pleiotropic effects that result in cardiovascular improvement. The aim of the present study was to evaluate the effects of metformin treatment on vascular dysfunction in ovariectomized rats. At 8 weeks of age, female Wistar rats were subjected to ovariectomy or a sham surgery. After 21 days, the animals were divided into three groups: SHAM (sham-operated rats), OVX (ovariectomized rats) and MET (ovariectomized rats treated with metformin at 300 mg/kg of body weight per day), and treated for 14 days. The vasorelaxation responses to ACh (acetylcholine) and SNP (sodium nitroprusside) were evaluated in mesenteric vascular beds, oxidative stress was evaluated and Western blot analysis of eNOS (endothelial NO synthase) and the NADPH oxidase Nox2 was performed. ACh-induced relaxation was reduced in the OVX group and partially restored in the MET group. L-NAME (NG-nitro-L-arginine methyl ester) attenuated and equalized the ACh-induced response in all groups. Attenuation of the ACh-induced responses by 4-aminopyridine (a blocker of voltage-gated potassium channels) was greater in the MET group compared with the OVX group. The SNP-induced responses were reduced in the OVX group and restored in the MET group. Inhibition of NADPH oxidase by apocynin (10 μM) restored the SNP-induced responses in the OVX group, enhanced these responses in the MET group and had no effect in the SHAM group. The OVX group exhibited reduced levels of eNOS protein and increased levels of oxidative stress and Nox2 protein; metformin treatment corrected all of these parameters. In conclusion, the pathophysiological changes observed in the mesenteric beds of ovariectomized rats were ameliorated by metformin. If this translates to humans, metformin could have additional benefits for post-menopausal women treated with this drug for glycaemic control.
authors: *Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
authors: Phablo Wendell C
authors: PW
authors: Oliveira
authors: *Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
authors: Glauciene J
authors: GJ
authors: de Sousa
authors: *Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
authors: Izabela F
authors: IF
authors: Caliman
authors: *Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
authors: Aline Z
authors: AZ
authors: Lamas
authors: †Biological and Health Sciences, Federal Institute of Espírito Santo, Vitória, Espírito Santo, Brazil.
authors: Ana Raquel
authors: AR
authors: Santos de Medeiros
authors: Tadeu U
authors: TU
authors: de Andrade
authors: *Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
authors: Glaucia R
authors: GR
authors: de Abreu
authors: *Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
authors: Suely G
authors: SG
authors: de Figueiredo
authors: *Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
authors: Nazaré S
authors: NS
authors: Bissoli
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D014652:Vascular Diseases / Q000188:drug therapy*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D007004:Hypoglycemic Agents; D008562:Membrane Glycoproteins; D008687:Metformin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000109:Acetylcholine