Role of Nitric Oxide in the Progression of Severe Acute Pancreatitis

Abstract

A growing amount of evidence has been presented that nitric oxide (NO) exerts various effects in the pathobiology of acute pancreatitis, but the role of NO during acute pancreatitis remains controversial. To investigate the role of NO during the progression of severe acute pancreatitis, we employed rat taurocholate (TCA)-induced pancreatitis. Serum nitrate and nitrite (NOx) concentrations increased during the course of TCA pancreatitis. The elevation of serum was significantly inhibited by the administration of specific NOS inhibitors (both nonselective NOS inhibitors and iNOS selective inhibitor). Despite the strong inhibition of NO production, these agents did not ameliorate the gross pathological appearance of the pancreas or reduce the elevation of serum amylase. In addition, nonselective NOS inhibitors worsened the hematocrit, myeloperoxidase activity in the lung, and mortality during pancreatitis. Although iNOS selective inhibitor did not affect the hematocrit and mortality during pancreatitis, it significantly aggravated myeloperoxidase activity in the lung. The supernatant of TCA pancreatitis ascites could induce iNOS in the peritoneal macrophages of normal rats in vitro, whereas, it decreased the endothelial NOS mRNA level in umbilical vein endothelial cells (HUVECs). The expression of adhesion molecules and interleukin-8 in HUVECs induced by ascitic fluid were attenuated by NO donor, whereas the NOS inhibitor augmented them. The results suggest that NO plays a protective role during the progression of acute pancreatitis through modulation of the leukocytes and endothelial cell systems.