Effect of nitric oxide synthase inhibition on hemoglobin-oxygen affinity and lipid peroxidation in rabbits during fever.
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 microg/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 (P(50)), concentrations of conjugated dienes, Schiff bases and alpha-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(omega)-nitro-L-arginine; 5x10(-3) M) reduced the lipopolysaccharide-induced rise in body temperature. After 180 min the actual P(50) 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 P(50) and conjugated dienes, Schiff bases, alpha-tocopherol and catalase.


CONCLUSIONS
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.
Zinchuk
V
V
Department of Physiology, Grodno Medical Institute, Grodno, Belarus. zinchuk@ggmi.belpak.grodno.by
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005334:Fever / Q000209:etiology / Q000378:metabolism*; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000378:metabolism*; D011817:Rabbits
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010108:Oxyhemoglobins; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase