Thesis (M.Sc. in Pharm.)--Chulalongkorn University, 2004

Metformin is antihyperglycemic drug with antihypertensive property. In this study, the effects of metformin on the contractility of vascular smooth muscle of isolated rat aorta in the presence and absence of endothelium were investigated. The contactile response were measured isometrically. These results showed that metformin significantly inhibited the contraction induced by noradrenaline and caffeine. In addition, metformin directly caused significant vasodilation effect (p< 0.05). The percentage of maximal relaxation in endothelium-intact (32.96 +- 2.84 %, n = 16) was significantly higher than that of endothelium-denuded (14.93 +- 3.07 %, n = 7) (p< 0.05). In addition, methylene blue, atropine and L-NAME significantly inhibited the relaxant effect of metformin in endothelium-intact segment (p< 0.05). However indomethacin, propranolol, TEA, 4-AP and glibenclamide had no effect on metformin-mediated relaxation. In conclusion, metformin may affect vascular contractility by induced endothelium-dependent and endothelium-independent relaxation. Metformin-induced relaxation may be mediated direct activation of cholinergic receptor on the endothelium to initiate the NO-cGMP pathway.