Endothelin Mediated Nitric Oxide Effects in Ischemia-Reperfusion Associated with Pancreas Transplantation

Research paper by Georgina Hotter, Felip Pi, Carles Sanz, Carmen Peralta, Emilio Gelpi, Francisco Badosa, Laureano Fernandez-Cruz, Joan Rosello-Catafau

Indexed on: 01 Dec '98Published on: 01 Dec '98Published in: Digestive Diseases and Sciences


Formation of nitric oxide (NO) inischemia-reperfusion (I-R) associated with pancreastransplantation could modulate the inflammatoryresponse. In this sense, previous studies havedemonstrated the action of NO on vasoactive substances likeprostacyclin or endothelin. The present study wasdesigned to evaluate the contribution of endothelin tothe inflammatory events induced by NO in the I-R processassociated with pancreas transplantation. For thispurpose, pancreatic levels of endothelin, neutrophilinfiltration, and prostacyclin were evaluated in anexperimental model of pancreas transplantation afterinhibition of NO synthesis or after NO inhibition plusaddition of endothelin. Results show significantposttransplantation increases in endothelin, neutrophilinfiltration, and prostacyclin production. Theseincreases were prevented by NO inhibition. Endothelinadministration plus nitric oxide inhibition reversedthis effect, resulting in an increase in myeloperoxidaseand 6-ketoprostaglandin F1α. Theseresults suggest that the proinflammatory effects of NO in I-Rassociated with pancreas transplantation are mediated bythe induction of endothelin generation.