ENDOTHELIN-1 MEDIATED FEMORAL ARTERY CONTRACTION AND METHYLPREDNISOLONE

Abstract

Introduction: The aim of this study was to investigate if steroids enhance the vasoconstrictive effect of endothe-lin-1 (ET-1) on femoral arteries.

Materials and Methods: Ten female Wistar rats 59 to 88 days of age and 238 to 310 g of body weight, were used. Forty femoral artery segments were harvested. These arterial segments were mounted as ring preparations on a small vessel myograph. Two vessels from each animal were randomized to incubation with methylprednisolone 5 μg/ml [1] while the other 2 vessels were incubated with placebo. The arteries were stimulated cumulatively with endothelin-1. Isometric wall tension was quantified by the EC50; the vasoconstrictor concentration resulting in half maximal contraction.

Results: Thirty-eight arteries could be harvested in total; 20 were randomized to steroid treatment while 18 served as controls. The endothelin-1 dose-response curve displayed a stronger contraction for the steroid group in relation to the controls with increasing doses of ET-1. The EC50 of 4.4*10⁻⁸ M ± 1.8*10⁻⁸ M for the steroid vessels was lower compared to 5.9*10⁻⁸ M ± 3.4*10⁻⁸ M for the controls (mean ±SD; n.s.).

Discussion: Endothelin-1 is a potent vasoconstrictor. This study showed that incubation with methylprednisolone enhanced ET-1 mediated contraction of femoral arteries which can diminish blood flow within the vascular bed supplying the femoral head. This may be a relevant cofactor in the early pathogenesis of steroid-associated femoral head necrosis.