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Metformin Improves Endothelial Function and Reduces Blood Pressure in Diabetic Spontaneously Hypertensive Rats Independent from Glycemia Control: Comparison to Vildagliptin

Hamidi Shishavan, M., Henning, R. H., van Buiten, A., Goris, M., Deelman, L. E. & Buikema, H., 8-Sep-2017, In : Scientific Reports. 7, 1, 12 p., 10975.

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Metformin confers vascular benefits beyond glycemia control, possibly via pleiotropic effects on endothelial function. In type-1-diabetes-mellitus (T1DM-)patients metformin improved flow-mediated dilation but also increased prostaglandin(PG)-F-2 alpha, a known endothelial-contracting factor. To explain this paradoxical finding we hypothesized that metformin increased endothelial-vasodilator mediators (e.g. NO and EDHF) to an even larger extent. Spontaneously-hypertensive-rats (SHR) display impaired endothelium-dependent relaxation (EDR) involving contractile PGs. EDR was studied in isolated SHR aortas and the involvement of PGs, NO and EDHF assessed. 12-week metformin 300 mg/kg/day improved EDR by up-regulation of NO and particularly EDHF; it also reduced blood pressure and increased plasma sulphide levels (a proxy for H2S, a possible mediator of EDHF). These effects persisted in SHR with streptozotocin (STZ)-induced T1DM. Vildagliptin (10 mg/kg/day), targeting the incretin axis by increasing GLP-1, also reduced blood pressure and improved EDR in SHR aortas, mainly via the inhibition of contractile PGs, but not in STZ-SHR. Neither metformin nor vildagliptin altered blood glucose or HbA(1c). In conclusion, metformin reduced blood pressure and improved EDR in SHR aorta via up-regulation of NO and particularly EDHF, an effect that was independent from glycemia control and maintained during T1DM. A comparison to vildagliptin did not support effects of metformin mediated by GLP-1.

Original languageEnglish
Article number10975
Number of pages12
JournalScientific Reports
Volume7
Issue number1
Publication statusPublished - 8-Sep-2017

    Keywords

  • HYDROGEN-SULFIDE, VASOCONSTRICTOR PROSTANOIDS, INSULIN-RESISTANCE, CONTROLLED-TRIAL, DYSFUNCTION, GLUCOSE, NEPHROPATHY, ASSOCIATION, METABOLISM, INHIBITORS

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