EVALUATION OF INFLUENCE OF 24-HOUR COLD PRESERVATION ON ENDOTHELIN PRODUCTION AND ON ENDOTHELIN RECEPTORS IN THE BONE VASCULATURE

Endothelin-1 is a vasoactive peptide produced by the vascular endothel ium. It is one of the most potent endogenous vascular smooth muscle co nstrictors. Two subtypes of the endothelin receptor have been cloned a nd sequenced and denoted endothelin-A and endothelin-B. The aim of thi s study was to define the influence of cold ischemia on the production of endothelin-1 and on the endothelin receptors. Two different preser vation techniques (cold storage only and cold storage with microperfus ion with University of Wisconsin solution) also were compared. The stu dy was performed in an in vitro bone perfusion model to isolate the va scular endothelium from blood components. The production of endothelin -1 by the bone vasculature was not altered after 24 hours of cold isch emia. No contractions were observed with S6c, a selective endothelin-B agonist, and this effect was not influenced by cold ischemia. The res ponse mediated by the endothelin-A receptor was increased significantl y, an effect that was not influenced by preservation with University o f Wisconsin solution. This latter finding was the only significant alt eration in the vascular function detected in the in vitro model after 24 hours of cold ischemia. With regard to the pharmacologic properties of endothelin-1, this mediated response could be implicated in the pa thogenesis of vasospasm.