CONICET | Buscador de Institutos y Recursos Humanos

Aim: We previously reported that atrial natriuretic peptide (ANP) reduces serumamylase and intrapancreatic trypsinogen activation in the onset of acute pancreat i-tis whereas secretin increases them. In the present work, we sought to establishthe effect of ANP and secretin on the inflammatory response and cell death inexperimental acute pancreatitis.Methods: The expression and activity of key inflammatory mediators and apop-tosis were evaluated in the presence or absence of the atrial peptide, secretin orboth in cerulein-induced acute pancreat itis in rats. Also, ultrastructural changes inpancreatic acinar cells were assessed by transmission elect ron microscopy.Results: ANP signi fican tly redu ced NF-jB activation and TNF-a intrapancreaticlevels. Furthermore, it decreased inducible nitric oxide synthase and cyclooxygenase 2expression and activity while it diminished myeloperoxidase activity. ANP also stimu-lated apoptosis as shown by caspase-3 expression and activation as well as TUNELas say . These findings correlated well with the ultrastruc tur al changes observed in theexocrine pancreas. Although secretin reduced various inflammatory markers, it alsodiminished caspase-3 activation and the overall response was the aggravation of thedisease as reflected by the ultrastructural alterations of pancreatic acinar cells. In thepresence of ANP, various effects evoked by secretin were antagonized.Conclusion: Present findings show that ANP significantly attenuated the severityof acute pancreatitis in the rat by inducing apoptosis and reducing the inflamma-tory response and further suggest that ANP may have eventual therapeutic impli-cations in the disea se and/or in medical interventions at risk of its developing likeendoscopic retrograde cholangiopancreatography