Femoral artery constriction by norepinephrine is enhanced by methylprednisolone in a rat model

Background: Corticosteroids are associated with femoral head osteonecrosis and arterial hypertension. The pathomechanism of femoral head osteonecrosis is often attributed to ischemia. The aim of this study was to investigate if corticosteroids directly constrict the femoral artery or if they have a permissive effect on norepinephrine and endothelin-1-induced vasoconstriction. Methods: Femoral artery segments were harvested from twenty Wistar rats and mounted as ring preparations on a small-vessel myograph for the purpose of making isometric force measurements. For the norepinephrine study, twenty femoral artery segments from ten rats were stimulated cumulatively with norepinephrine before and after incubation with methylprednisolone (5 mu g/mL). For the endothelin-1 study, forty femoral artery segments from ten rats were used. The four artery segments from each animal were randomized by pairs to either a corticosteroid treatment group (5 mu g/mL methylprednisolone incubation, n = 20) or a control group (placebo incubation, n = 18, as two of the twenty control-group vessels did not meet protocol requirements). Isometric wall tension was plotted and quantified by the EC50 (the plasma concentration of endothelin-1 required for obtaining 50% of maximal constriction in vivo). Results: In the norepinephrine-stimulated group, incubation with methylprednisolone did not directly induce any vasoconstriction but did enhance norepinephrine-elicited vasoconstriction. The norepinephrine dose-response curve displayed a shift to the left after incubation with methylprednisolone. This shift was reflected by a significantly lower mean EC50 of 9.5 x 10(-7) M +/- 5.1 x 10(-7) M after methylprednisolone incubation compared with a mean of 2.5 x 10(-6) M +/- 1.1 x 10(-6) M before incubation (p < 0.005). In the endothelin-1-stimulated group, the endothelin-1 dose-response curve displayed a tendency toward stronger contraction in the vessels that were incubated with methylprednisolone, but this tendency did not reach significance. Conclusions: Incubation with methylprednisolone enhances norepinephrine-mediated contraction of the femoral artery in a rat model. Clinical Relevance: Vasoconstriction of the vascular bed supplying the femoral head can diminish femoral head blood flow, and this may be a factor in the early pathogenesis of corticosteroid-associated femoral head osteonecrosis.