We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation is significantly attenuated when SS-13BN/Mcwi rats are fed a high salt diet. This effect was associated with a large increase in endothelial cell (EC) apoptosis. We hypothesized that the low levels of angiotensin II (ANGII) during high salt diet would increase EC apoptosis and consequently diminish the angiogenic response. To test this hypothesis a series of in vitro and in vivo studies were performed. EC apoptosis and viability were evaluated after incubation with ANGII under serum free condition. After 24h of incubation, ANGII increased EC viability and Bcl-2/Bax ratio along with a dose-dependent decrease in EC apoptosis. This effect was blocked by the ANGII type 1 receptor antagonist losartan. In order to confirm our in vitro results, ANGII (3ng/kg/min) was chronically infused into rats fed a high salt diet (4% NaCl). AngII decreased EC apoptosis and produced a significant increase (40%) in skeletal muscle angiogenesis after electrical stimulation. These in vivo results were in agreement with our in vitro results and demonstrate that the attenuation of ANGII levels during high salt diet may induce EC apoptosis and consequently block the angiogenesic response induced by electrical stimulation. Further, under normal conditions ANGII increases EC viability and protects EC from apoptosis possibly by inactivation of mitochondrial apoptotic pathway.