The Journal of Bone and Joint Surgery (American). 2006;88:162-166.
doi:10.2106/JBJS.F.00452
© 2006 The Journal of Bone and Joint Surgery, Inc.
Femoral Artery Constriction by Norepinephrine Is Enhanced by Methylprednisolone in a Rat Model
Wolf Drescher, MD, PhD,
Deike Varoga, MD,
Thoralf R. Liebs, MD,
Janne Lohse,
Thomas Herdegen, MD, PhD,
Joachim Hassenpflug, MD, PhD and
Thomas Pufe, PhD
Corresponding author: Wolf Drescher, MD, PhD Department of Orthopaedic
Surgery, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel,
Germany. E-mail address:
wolfdrescher{at}hotmail.com
In support of their research for or preparation of this manuscript, one or
more of the authors received grants or outside funding from the German
Research Foundation (DFG), grants no. DR 449/2-1 and VA 220/2-1. None of the
authors received payments or other benefits or a commitment or agreement to
provide such benefits from a commercial entity. No commercial entity paid or
directed, or agreed to pay or direct, any benefits to any research fund,
foundation, educational institution, or other charitable or nonprofit
organization with which the authors are affiliated or associated.
Background: Corticosteroids are associated with femoral head
osteonecrosis and arterial hypertension. The patho-mechanism 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
µg/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 µg/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.

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