Mechanism of action of alendronate in vascular system

CUTINI P.; RAUSCHEMBERGER M.B.; CAMPELO A.; MASSHEIMER V.

Ciudad Autónoma de Buenos Aires

Congreso; XXX Reunión Anual de la Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM); 2013

Bisphosphonates (BP) are frequently used in postmenopausal osteoporosis treatment. Although the risks attributed, hormone replacement therapy with estrogens combined with synthetic progestins remains as an alternative therapy to counteract menopause signs and symptoms. The aim of this work was to investigate the mechanism of action of alendronate (ALN) in vascular tissue in the presence or absence of synthetic or endogenous ovarian hormones such as estrone (E1) or medroxyprogesterone acetate (MPA). Endothelial cell (EC) and vascular smooth muscle cell (VSMC) cultures obtained from aortic strips of Wistar rats were employed. ALN treatment markedly increased EC nitric oxide (NO) production. In the presence of a MEK inhibitor (PD98059), the stimulatory action of ALN on NO was suppressed (220 ± 20 vs 345 ± 38, 210 ± 21 vs 221 ± 18 nmol de NO/mg prot; C vs ALN, C + PD vs ALN + PD; p < 0.05). The effect of ALN on NO synthesis was dependent on extracellular calcium influx, since preincubation of EC with the channel blocker verapamil (V) blunted BPs action (238 ± 19 vs 245 ± 16 nmol de NO/mg prot; C + V vs ALN + V; p < 0.05). In combined treatments, the simultaneous exposure to ALN + E1 enhanced the individual effect of each agonist on NO synthesis (90, 60, 58% above control; ALN + E1, ALN, E1; p < 0.05). Higher improvement effect was obtained with ALN + MPA co-treatments (56, 80, 250% above control; ALN, MPA, ALN + MPA; p < 0.02). Using wound healing assays, we showed that 48 h of exposure to ALN partially prevents MPA-induced cell motility (344 ± 39 vs 219 ± 24 cells/field; MPA vs MPA + ALN; p < 0.001). In conclusion, BP has a positive effect on vascular homeostasis, improved by the presence of ovarian hormones.