METFORMIN ATTENUATES AGONIST-STIMULATED CALCIUM TRANSIENTS IN VASCULAR SMOOTH-MUSCLE CELLS

Metformin, an antidiabetic agent that increases insulin sensitivity, h as been shown to lower blood pressure. However, the mechanism of actio n of metformin in vascular smooth muscle (VSM) cell is not fully under stood. We have tested the hypothesis that metformin produces vascular changes by direct interaction with VSM cells by investigating its effe ct on platelet-derived growth factor (PDGF)- and angiotensin II (ANG I I)-stimulated intracellular calcium concentration ([Ca2+](i)) and VSM cell proliferation in response to PDGF in cultured cells. VSM cells we re cultured from rat thoracic aorta and [Ca2+](i) was estimated in sin gle cells by image analysis. Treatment of VSM cells with 1 or 2 mu g/m l metformin significantly decreased (p < 0.05) PDGF- or ANG II-stimula ted [Ca2+](i). Treatment of VSM cells with 1, 2, 5, or 10 mu g/ml metf ormin had no significant effect on PDGF-stimulated [H-3]-thymidine inc orporation. However, metformin at pharmacological doses of 20 and 50 m u g/ml significantly reduced (p < 0.05) PDGF-stimulated thymidine inco rporation. We conclude that metformin mediates its vascular effects by attenuating agonist-stimulated [Ca2+](i).