Activity of Oxidative Stress and Damage to Vascular Endothelium in Rats with Experimental Peritonitis Under Administration of NO-Syntase Inhibitors |Biomedgrid

Background: The high lethality in peritonitis and the lack of data on the role of various NO-synthase isoforms in its pathogenesis suggests the advisability of the research to study the effects of NO-synthase (NOS) inhibitors. Objective: The aim of the research was to study the activity of oxidative stress and state of vascular endothelium in rats with experimental peritonitis under administration of NO-syntase inhibitors. Material and Methods: The research was carried out on male rats (n=72), divided into 4 series which were injected intraperitoneally with 0.6ml/100g: 1st series (control)-0,85% NaCl; 2nd series (experimental peritonitis, EP)-15% fecal suspension; 3rd series (EP+L-NAME)-15% fecal suspension with intramuscular injection of Nώ-nitro-L-arginine methyl ester, L-NAME (10mg/ kg); 4th series (EP+AG)-15% fecal suspension with intramuscular administration of aminoguanidine, AG (15mg/kg). The content of nitrite/nitrates (NOx), malondialdehyde (MDA) and reduced glutathione (GSH) in blood plasma of rats, the quantity of circulating endothelial cells (CEC) in blood were analyzed in half a day, 1 day and 3 days of EP. Results: An increase in the level of NOx and MDA, a decrease in [GSH] in blood plasma, an increase in amount of CEC in the blood of rats with EP were detected. Unidirectional changes, however, to a greater extent, were observed in EP under administration of L-NAME. The administration of AG resulted in decrease in level of NOx and MDA, an increase in [GSH] in blood plasma, a decrease in the amount of CEC in blood. Conclusion: The course of acute EP was characterized by significant increase in level of NOx, development of oxidative stress and damage to endothelium of blood vessels. The administration of non-selective NOS inhibitor, L-NAME, aggravated the severity of changes in EP, that may be explained by inhibition of endothelial NOS with progression of microcirculatory disorders. The corrective effect of AG in EP was manifested by a decrease in [NOx], oxidative stress activity and degree of damage to vascular endothelium, which may be a consequence of the suppression of cytotoxic nitric oxide overproduction.