Nitric oxide is a versatile molecule, with its actions ranging from haemodynamic regulation to anti-proliferative effects on vascular smooth muscle cells. Nitric oxide is produced by the nitric oxide synthases, endothelial NOS (eNOS), neural NOS (nNOS), and inducible NOS (iNOS). Constitutively expressed eNOS produces low concentrations of NO, which is necessary for a good endothelial function and integrity. Endothelial derived NO is often seen as a protective agent in a variety of diseases. This review will focus on the potential protective role of eNOS. We will discuss recent data derived from studies in eNOS knockout mice and other experimental models. Furthermore, the role of eNOS in human diseases is described and possible therapeutic intervention strategies will be discussed.

Nitric oxide (NO¡) is produced by NO synthases (NOS)and can interact with reactive oxygen species (ROS) to form peroxynitrite, which induces protein damage by formation of nitrotyrosine. NO¡ has a promotional effect on acute rejection. To investigate the role of NO¡ during chronic renal transplant failure (CRTF), we studied the expression of eNOS and iNOS in conjunction with H 2 O 2 production and the formation of nitrotyrosines. Nephrectomy material from 10 patients and 10 control kidneys was used in this study. Expression of iNOS, eNOS, nitrotyrosine and the presence of ROS-producing cells and macrophages were determined using immunohistochemistry. INOS expression in nonsclerosed glomeruli and interstitium was significantly increased in patients with CRTF (p ∞0.05). Glomerular eNOS expression was decreased in patients with CRTF compared with glomeruli of control kidneys (p ∞0.01). Nitrotyrosine and ROS positive cells were significantly increased in CRTF in the interstitium (p ∞0.05), but not in glomeruli. In summary, we found a marked interstitial increase in iNOS protein expression together with a decrease in glomerular eNOS expression in CRTF patients, associated with a significant increment in ROS and nitrotyrosine-positive cells in the interstitium. Our results suggest that loss of NO¡ production by glomerular eNOS in conjunction with an increased NO¡ production by interstitial iNOS, together with the formation of ROS and nitrotyrosine, is involved in the pathogenesis of CRTF.

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TIAF-1 mRNA and protein are predominantly up-regulated in kidney and liver allografts with chronic rejection. This does not seem to be related to the cyclosporine A therapy. Expression of TIAF-1 in the lymphocytes during chronic allograft rejection may be related to the predominance of a Th2 response in this condition. The expression in the transplanted tissue may protect these cells from apoptosis.

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