Background & aims: Patients and rats with cirrhosis and ascites are prone to develop peritonitis. The aim of this study was to assess whether peritoneal macrophages of cirrhotic rats without peritoneal infection produce nitric oxide and express inducible NO synthase (iNOS).
Methods: NO2- accumulation produced by macrophages from control rats and cirrhotic rats with ascites was determined. iNOS messenger RNA and protein expression were analyzed by Northern and Western blot and immunocytochemical analysis. The in vivo effects of inhibiting iNOS were investigated by giving the specific iNOS inhibitor L-N-(1-iminoethyl)-lysine (L-NIL) or sterile saline to 9 and 7 cirrhotic rats with ascites, respectively.
Results: Cirrhotic macrophages produced NO2- that was around fourfold greater than that of control macrophages after 30 hours in culture. Northern and Western blot and immunocytochemical analysis showed the presence of iNOS messenger RNA and protein in macrophages of cirrhotic rats. Ascites cultures were positive in all rats administered L-NIL and negative in those administered saline.
Conclusions: Macrophages of cirrhotic rats produce NO and express iNOS messenger RNA and protein, and these changes are not a consequence of overt bacterial infection. Because iNOS inhibition results in peritoneal infection, these results suggest that iNOS induction in macrophages of cirrhotic rats is a host defense response to prevent bacterial peritonitis.