INHIBITION OF NITRIC-OXIDE SYNTHESIS ENHANCES THE EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE MESSENGER-RNA AND PROTEIN IN A MODEL OF CHRONIC LIVER INFLAMMATION

In septic shock the inhibition of inducible nitric oxide synthase (NOS ) could be of therapeutic value. However, side effects have to be inve stigated. Therefore we studied the effects of chronic NOS inhibition o n the level of iNOS expression in a model of chronic liver inflammatio n induced by Corynebacterium parvum (C. parvum) which causes sustained iNOS expression in the liver. NOS inhibitors decreased the rise in pl asma levels and urinary excretion of nitrite/nitrate by about 50%; how ever, iNOS mRNA and protein were increased to 200% and 150%, respectiv ely. Thus chronic inhibition of NOS can result in an increase in iNOS mRNA level and protein under conditions when iNOS is expressed. This c ould result in an overproduction of NO upon removal of the NOS-inhibit or. (C) 1994 Academic Press, Inc.