Inducible nitric oxide synthase in the lung and exhaled nitric oxide after hyperoxia.

The effect of hyperoxia on nitric oxide (NO) production in intact animals is unknown. We described the effects of hyperoxia on inducible nitric oxide synthase (iNOS) expression and NO production in the lungs of rats exposed to high concentrations of oxygen. Animals were placed in sealed Plexiglas chambers and were exposed to either 85% oxygen (hyperoxic group) or 21% oxygen (negative control group). Animals were anesthetized after 24 and 72 h of exposure and were ventilated via a tracheotomy. We measured NO production in exhaled air (E(NO)) by chemiluminescence. The lungs were then harvested and processed for detection of iNOS by immunohistochemistry and Western blotting analysis. The same experiments were repeated in animals exposed to hyperoxia for 72 h after they were infused with L-arginine. We used rats that were injected intraperitoneally with Escherichia coli lipopolysaccharide to induce septic shock as a positive control group. Hyperoxia and septic shock induced expression of iNOS in the lung. However, E(NO) was elevated only in septic shock rats but was normal in the hyperoxic group. Exogenous infusion of L-arginine after hyperoxia did not increase E(NO). To exclude the possibility that in the hyperoxic group NO was scavenged by oxygen radicals to form peroxynitrite, lungs were studied by immunohistochemistry for the detection of nitrotyrosine. Nitrotyrosine was found in septic shock animals but not in the hyperoxic group, further suggesting that NO is not synthesized in rats exposed to hyperoxia. We conclude that hyperoxia induces iNOS expression in the lung without an increase in NO concentration in the exhaled air.

Adenovirus infection of the renal allograft with sparing of pancreas graft function in the recipient of a combined kidney-pancreas transplant.

We report a case of adenovirus infection of the renal allograft in a combined kidney/pancreas transplant recipient. The clinical presentation was renal allograft failure, which eventually reversed. The pancreatic graft function remained stable. A renal biopsy showed massive tubular necrosis associated with a prominent granulomatous reaction. The process had a striking regional distribution within the kidney with the injury and inflammation limited to the outer medulla. Adenovirus type 11 was isolated from renal tissue by culture, and adenovirus was demonstrated by immunofluorescence and electron microscopy in the kidney biopsy. Immunosuppression may result in unusual patterns of response to infectious agents. This case demonstrated tropism of the adenovirus to only selected tubules within the kidney, with sparing of other organ function including, specifically, the pancreas allograft. The differential diagnosis of a granulomatous reaction in the transplant kidney must be expanded to include viral infection, in particular, adenovirus.