The Effects of Nitric Oxide Synthase Inhibitors on Acute Necrotising Pancreatitis in Rats Etem Alhan, 1 Uzer Ku ¨c ¸u ¨ktu ¨lu ¨ 1 and Cengiz Erc ¸in 2 From the 1 Department of Surgery, Farabi Hospital, Medical Faculty, Karadeniz Technical University, Trabzon and 2 Department of Pathology, Medical Faculty, Kocaeli University, Kocaeli, Turkey Eur J Surg 1998; 164: 697–702 ABSTRACT Objective: To investigate the effects of the constitutive nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-Name) and the inducible NO synthase inhibitor amino ethyl-isothiourea (AE-ITU) on acute necrotising pancreatitis (ANP) in rats. Design: Laboratory study. Setting: Medical school, Turkey. Main outcome measures: Morbidy, mortality, effects on activities of various enzymes, and histological picture. Results: NO inhibitors increased the mortality (from 8/15, 53%, for ANP plus saline, to 12/15, 80%, for ANP plus L-Name, and 13/15, 87%, for ANP plus AE-ITU and serum amylase activity, but had no effects on serum calcium concentrations, volume of ascites, or degree of pancreatic damage. L-Name caused hypoglycemia, and AE-ITU reduced activites of lactate dehydrogenase and liver transaminases, and concentrations of urea and creatinine. Conclusions: Constitutive NO synthase inhibition worsens the course of ANP, and inducible NO inhibition has beneficial effects on various systems. Key words: acute pancreatitis, nitric oxide inhibitor. INTRODUCTION Nitric oxide (NO) is produced from L-arginine by various cells including vascular endothelial cells, macrophages, Kupffer cells, neurones, smooth muscle cells, cardiac myocytes, and hepatocytes (17). It is generated by NO synthase, which exists in constitutive and inducible isoforms. The constitutive form has been isolated from vascular endothelial cells and neurones (17), and the inducible isoforms have been cloned from various types of cell including macrophages, smooth muscle cells, chondrocytes, and hepatocytes (17). Roles attributed to NO include neurotransmission, host defence by antimicrobial activity, regulation of basal blood pressure, inhibition of platelet aggregation, and several leucocyte-dependent inflammatory pro- cesses (16, 17). In the pancreas, NO synthase may have a physiolo- gical role in cells and neurones. (16, 27, 30). Nitroso compounds generate NO either spontaneously (sodium nitroprusside–SNP) or enzymatically (glyceryl trini- trate) and are therefore considered to be NO donors. Previous studies have shown that NO donors seem to stimulate pancreatic secretion (16, 21, 36). The effects of NO on the inflammatory processes and the regulation of vascular tone suggest that NO donors or inhibitors can be used in the treatment of acute pancreatitis when vascular function is impaired (2, 9). A NO synthase inhibitor will reduce formation of pancreatic oedema and vascular permeability during acute pancreatitis (1). On the other hand, NO is not involved in the progression from oedematous to haemorrhagic pancreatitis (35). However, the effect of NO on the course of acute pancreatitis is contro- versial. Malero et al showed that NO donor drugs may improve the course of acute pancreatitis (22), whereas Lomis et al suggested that NO synthase inhibitors prevented the progressive and severe hypotension associated with pancreatitis in rats (20). The aim of the present study was to investigate the effects of the constitutive NO synthase inhibitor NG- nitro L-arginine methyl ester (L-Name) and inducible NO synthase inhibitor amino-ethyl-isothiourea (AE- ITU) on the course of acute necrotising pancreatitis (ANP) in rats. MATERIAL AND METHODS Male Sprague-Dawley rats (350–390 g) were housed individually in hanging wire-bottomed cages and maintained at 21° (1°) C using a 12 hour light/dark cycle. The animals were given a standard rat chow, and 1998 Scandinavian University Press. ISSN 1102–4151 Eur J Surg 164 ORIGINAL ARTICLE