Effects of acute rejection on L-arginine/iNOS pathway in canine heart transplantation.

摘要

BACKGROUND: The inflammatory process resulting from ischemia-reperfusion and acute rejection is a strong modulator of the endothelial nitric oxide synthase expression of both constitutive and inducible isoforms. OBJECTIVE: To assess the expression of the endothelial constitutive nitric oxide synthase (ecNOS) and inducible nitric oxide synthase (iNOS) activity in conductance coronary arteries after reperfusion and acute rejection in the canine heart transplantation setting. METHODS: Expression of ecNOS and iNOS was evaluated in two groups of mongrel dogs (n=7) that underwent heterotopic heart transplantation without immunosuppression. The first group was studied after 24 h of reperfusion and the second after five days of acute untreated rejection. A third group (n=7) consisting of normal unoperated dogs was used as control. Functional vascular status of iNOS isoforms was studied in organ chambers, and tissue enzyme expression by histological and immunohistochemical studies. RESULTS: At harvest, vonWillebrand factor was present on the coronary endothelium of all groups. Both transplanted groups displayed iNOS and ecNOS expression by immunohistochemical study. The control group only displayed ecNOS expression. L-arginine induced endothelium-dependent relaxations in group 1 and group 2 but not in the control group. This was inhibited by the iNOS inhibitor aminoguanidine. Endothelium-independent contractility and relaxation were unaffected. CONCLUSIONS: In this experimental setting, a specific endothelial expression of iNOS was observed early on after acute rejection. The functional aspect of this endothelial iNOS expression was reversible with aminoguanidine.