Endothelin mediated nitric oxide effects in ischemia-reperfusion associated with pancreas transplantation

Formation of nitric oxide (NO) in ischemia-reperfusion (I-R) associated wit h pancreas transplantation could modulate the inflammatory response. In thi s sense, previous studies have demonstrated the action of NO on vasoactive substances like prostacyclin or endothelin. The present study was designed to evaluate the contribution of endothelin to the inflammatory events induc ed by NO in the I-R process associated with pancreas transplantation. For t his purpose, pancreatic levels of endothelin, neutrophil infiltration, and prostacyclin were evaluated in an experimental model of pancreas transplant ation after inhibition of NO synthesis or after NO inhibition plus addition of endothelin. Results show significant posttransplantation increases in e ndothelin, neutrophil infiltration, and prostacyclin production. These incr eases were prevented by NO inhibition. Endothelin administration plus nitri c oxide inhibition reversed this effect, resulting in an increase in myelop eroxidase and 6-keto-prostaglandin F-1 alpha. These results suggest that th e proinflammatory effects of NO in I-R associated with pancreas transplanta tion are mediated by the induction of endothelin generation.