Efectos vasculares de raloxifeno y alendronato

RAUSCHEMBERGER M. BELÉN; CUTINI PABLO; SANDOVAL MARISA; MASSHEIMER VIRGINIA

Actualizaciones en Osteología

Asociación Argentina de Osteología y Metabolismo Mineral

Lugar: Rosario; Año: 2013 vol. 9 p. 245 - 267

1669-8975

The aim of this work was to study and compare the vascular effects of two drugs frequently used osteoporosis treatment, the estrogen receptor modulator raloxifene and the bisphosphonate alendronate. We investigate the in vitro actions of raloxifene and alendronate on key cellular processes involved in vascular homeostasis such as the bioavailability of nitric oxide, and monocyte-platelet-endothelium interactions. Using endothelial cells cultures we found that, both drugs significantly enhanced nitric oxide production (56; 64% over control, raloxifene; alendronate respectively). The mechanism of action evoked by each drug was studied employing an estrogen receptor antagonist (ICI 182780 compound), and specific MAPK (PD98059) y PI3K (LY294002) inhibitors. The evidence obtained shows that estrogen receptor and PI3K mediated vascular raloxifene actions, meanwhile the effect of alendronate was dependent on MAPK signalling transduction pathway. When endothelial cells were incubated in high extracellular calcium concentrations, only alendronate was able to sustain its stimulatory action on nitric oxide synthesis. In platelet aggregation assays, we found that raloxifene exhibits a potent antiaggregatory action. To study monocyte-endothelium interactions, the effect of alendronate on monocyte adhesion to endothelial cells was evaluated. The bisphosphonate did not affect basal mononuclear adhesion, but significantly prevented monocyte adhesion induced by inflammatory environment represented by the presence of bacterial lipopolysaccharide. In summary, although both drugs elicited potential beneficial action on key process involved in vascular health, under stress conditions only alendronate maintain its capability to modulate the synthesis of the main vasoactive factor, nitric oxide.