Endothelin-1-induced femoral head epiphyseal artery constriction is enhanced by long-term corticosteroid treatment.
BACKGROUND
With regard to the pathogenesis of corticosteroid-associated femoral head osteonecrosis, only intravascular and extravascular factors have been discussed. Wall constriction of the lateral epiphyseal arteries, which are the main supplying arteries within the femoral head, has not previously been investigated. This study examined the effect of long-term corticosteroid treatment on vasoconstriction of the lateral epiphyseal arteries of the femoral head in a porcine model.


METHODS
The immature female Danish Landrace pig was chosen as the model for our study because femoral head osteonecrosis can be induced in this animal and because the lateral epiphyseal arteries of the femoral heads are of the appropriate size for myographic investigation. Twenty-four female Danish Landrace pigs (two siblings from each of twelve litters for a total of twelve sibling pairs) were divided by randomly separating the sibling pairs into two groups, with a total of twelve pigs in each group. One group of twelve animals received a daily dose of 100 mg of methylprednisolone orally for three months. The other group of twelve pigs served as controls and received no corticosteroids. After the animals were killed with an intravenous injection of pentobarbital, the lateral epiphyseal arteries of the femoral head were isolated from the cancellous bone. These arteries were mounted as ring preparations on a small-vessel myograph for measurement of isometric force development. The effects on the resected vessels of the vasoactive agents endothelin-1, noradrenaline, bradykinin, substance P, and nitrous oxide were investigated.


RESULTS
Vasoconstriction induced by increasing doses of endothelin-1 was increased after three months of methylprednisolone treatment compared with the vasoconstriction in vessels from control animals. Sensitivity to noradrenaline was not altered by this treatment. After submaximal precontraction by noradrenaline, vasorelaxation was elicited by substance P, nitrous oxide, and increasing doses of bradykinin without differences between the corticosteroid-treated and the control groups.


CONCLUSIONS
Endothelin-1-induced vasoconstriction of the epiphyseal arteries of the femoral head was increased in this corticosteroid-treated pig model. Such vasoconstriction may lead to a reduction in femoral head blood flow and to local ischemia and thus may be a newly described factor in the multifactorial pathomechanism of osteonecrosis of the femoral head.
Drescher
Wolf
W
Department of Orthopaedic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Michaelisstr. 1, D-24105 Kiel, Germany. wolfdrescher@hotmail.com
Li
Haisheng
H
Lundgaard
Anette
A
Bünger
Cody
C
Hansen
Ebbe-Stender
ES
D000818:Animals; D004334:Drug Administration Schedule; D019332:Endothelin-1 / Q000494:pharmacology; D004838:Epiphyses / Q000098:blood supply / Q000187:drug effects; D005260:Female; D005270:Femur Head / Q000098:blood supply* / Q000187:drug effects*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D005938:Glucocorticoids; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D008775:Methylprednisolone