INDUCIBLE AND ENDOTHELIAL NITRIC-OXIDE SYNTHASE EXPRESSION DURING DEVELOPMENT OF TRANSPLANT ARTERIOSCLEROSIS IN RAT AORTIC GRAFTS

In the vascular system, distinct isoforms of nitric oxide synthase (NO S) generate nitric oxide (NO), which acta as a biological messenger. I ts role in the development of transplant arteriosclerosis (TA) is stil l unclear. To investigate whether NO is involved in TA, we studied the expression of NOS isoforms, inducible NOS (iNOS) and endothelial NOS (eNOS), by immunohistochemistry and in situ hybridization during the f irst two post-transplantation months and their relation with cold isch emia (1 to 24 hours) and reperfusion injury using an aortic transplant ation model in the rat. We found an increased iNOS expression in the i ntima and adventitia and a decreased expression in the media, whereas eNOS expression was not significantly altered during the development o f TA. Co-localization studies suggested that iNOS-positive cells were vascular smooth muscle cells, monocyte-derived macrophages, and endoth elial cells. Prolonged ischemic storage time resulted in an increase i n eNOS expression in the neointima. In situ hybridization showed iNOS mRNA expression by vascular cells in the neointima and media. NO produ ced by iNOS and eNOS may be involved, at least in part, in the pathoge nesis of TA in aortic grafts. Additional studies are needed to confirm the modulatory mechanism of NO during the development of TA.