Effect of Nitric Oxide Synthase Inhibition on Hemoglobin-Oxygen Affinity and Lipid Peroxidation in Rabbits during Fever

Abstract

Background: Nitric oxide (NO) is one of the most important biologic messengers and takes part in the development of fever. It can influence on the body prooxidant-antioxidant balance by different ways including interaction with hemoglobin (Hb). Methods: The effects of nitric oxide synthesis inhibition on the febrile response, hemoglobin-oxygen affinity and parameters of lipid peroxidation were studied in rabbits with fever. The fever was induced by intravenous administration of lipopolysaccharide from Salmonella typhi (0.6 μg/kg). Mixed venous blood was taken before the administration and 60, 120 and 180 min after it. The following parameters were measured: half-saturation oxygen pressure (P₅₀), concentrations of conjugated dienes, Schiff bases and α-tocopherol in plasma and red blood cells, and activity of catalase in red blood cells. Results: The intravenous administration of the nitric oxide synthase inhibitor (N^ω-nitro-L-arginine; 5·10^–3 M) reduced the lipopolysaccharide-induced rise in body temperature. After 180 min the actual P₅₀ had decreased from 35.0 ± 1.7 to 29.4 ± 1.3 mm Hg. An increase in the lipid peroxidation parameters and a decrease of the antioxidant system indices were observed. The administration of L-arginine to prevent nitric oxide synthase inhibition was accompanied by a shift of the oxyhemoglobin dissociation curve rightwards, more marked activation of the free radical processes and a greater elevation of body temperature. The multiple regression analysis showed a close linear correlation between P₅₀ and conjugated dienes, Schiff bases, α-tocopherol and catalase. Conclusion: These results suggest that the increased hemoglobin-oxygen affinity found after the inhibition of nitric oxide synthesis lowers the oxygen flow to tissues and its fraction utilized in free radical oxidations, which finally causes a reduction of the fever response to the lipopolysaccharide.