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 (Nω-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.

Keywords:
Hemoglobin-oxygen affinity, Lipid peroxidation, Lipopolysaccharide, Fever, Nitric oxide
1.
Moncada S, Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002–2012.
2.
Palmer RMJ, Moncada S: A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 1989;158:348–352.
3.
Rees DD, Palmer RMJ, Schultz R, Hodson HF, Moncada S: Characterization of the inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol 1990;101:746–752.
4.
Nova E, Palmer RMJ, Moncada S: Inhibition of nitric oxide synthesis in septic shock. How much is beneficial? Lancet 1991;338:1555–1557.
5.
Pryor WA, Squadrito GL: The chemistry of peroxynitrite: A product from the reaction of nitric oxide with superoxide. Am J Physiol 1995;268:L699–L722.
6.
Beckman JS: The double-edged role of nitric oxide in brain function and superoxide-mediated injury. J Dev Physiol 1991;15:53–59.
7.
Wennmalm A, Benthin G, Edlund A, Jungersten L, Kieler-Jensen N, Lundin S, Westfelt UN, Petersson AS, Waagstein F: Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. Circ Res 1993;73:1121–1127.
8.
Kosaka H, Seiyama A: Physiological role of nitric oxide as an enhancer of oxygen transfer from erythrocytes to tissues. Biochem Biophys Res Commun 1996;218:749–752.
9.
Stamler JS, Jia L, Eu JP, McMahon TJ, Demchenko IT, Bonaventura J, Gernert K, Piantadosi CA: Blood flow regulation by S-nitrosohemoglobin in the physiological oxyten gradient. Science 1997;276:2034–2037.
10.
Borisiuk MV, Zinchuk VV: Analysis of the relationship between hemoglobin-oxygen affinity and lipid peroxidation during fever. Acta Biochim Pol 1995;42:69–74.
11.
Scheid P, Meyer M: Mixing technique for study of oxygen-hemoglobin equilibrium: A critical evaluation. J Appl Physiol 1978;45:616–622.
12.
Severinghaus JW: Blood gas calculator. J Appl Physiol 1966;21:1108–1116.
13.
Willford DC, Hill EP: Modest effects of temperature on the porcine oxygen dissociation curve. Respir Physiol 1986;64:113–123.
14.
Ahotupa M, Mantyla E, Peltola V, Puntala A, Toivonen H: Prooxidant effects of normobaric hyperoxia in rat tissues. Acta Physiol Scand 1992;145:151–157.
15.
Fletcher BL, Dillard CJ, Tappel AL: Fluorescent products of lipid peroxidation of mitochondria and microsomes. Anal Biochem 1973;52:1–9.
16.
Hansen LG, Warwick WJ: A fluorometric micromethod for serum vitamins A and E. Am J Clin Pathol 1969;4:538–541.
17.
Hanham AF, Dunn BP, Stich HF: Clastogenic activity of caffeic acid and its relationship to hydrogen peroxide generated during autooxidation. Mutat Res 1983;116:333–339.
18.
Layne EK: Spectrophotometric and turbidimetric methods for measuring protein. Methods Enzymol 1957;3:447–454.
19.
Zinchuk V: Correlation between hemoglobin oxygen affinity and activities of lipid peroxidation during hyperthermia. Ann Acad Med Bialostocensis 1995;40:290–295.
20.
Zinchuk V, Borisiuk M: The effect of NO synthase inhibition on blood oxygen-carrying function during hyperthermia in rats. Respir Physiol 1998;113:39–45.
21.
Vismont F, Zinchuk V: Effect of nitric oxide on lipid peroxidation activity and antioxidant factors during the hyperthermia. Ann AS Belarus 1999;43:84–87.
22.
Moran AP, Prendergast MM, Appelmelk BJ: Molecular mimicry of host structures by bacterial lipopolysaccharides and its contribution to disease. FEMS Immunol Med Microbiol 1996;16/2:105–115.
23.
Samaja M, Rovida E, Motterlini R, Tarantola M: The relationship between the blood oxygen transport and the human red cell aging process. Adv Exp Med Biol 1991;307:115–123.
24.
Glauser MP: The inflammatory cytokines. New developments in the pathophysiology and treatment of septic shock. Drugs 1996;52(suppl 2):9–17.
25.
Weihrauch D, Riedel W: Nitric oxide (NO) and oxygen radicals, but not prostaglandins, modulate fever. Ann NY Acad Sci 1997;813:373–382.
26.
Vodovotz Y, Bogdan C: Control of nitric oxide synthase expression by transforming growth factor-beta: Implications for homeostasis. Prog Growth Factor Res 1994;5:341–351.
27.
Wood SC: Interactions between hypoxia and hypothermia. Annu Rev Physiol 1991;53:71–85.
28.
Oleson JR: Eugene Robertson Special Lecture. Hyperthermia from the clinic to the laboratory: A hypothesis. Int J Hyperthermia 1995;11:315–322.
29.
Ayene IS, Dodia C, Fisher AB: role of oxygen in oxidation of lipid and protein during ischemia/reperfusion in isolated perfused rat lung. Arch Biochem Biophys 1992;296:183–189.
30.
Fercakova A, Halat G, Marsala M, Lukacova N, Marsala J: Graded postischemic reoxygenation reduces lipid peroxidation and reperfusion injury in the rabbit spinal cord. Brain Res 1992;593:159–167.
31.
Ihnken K, Morita K, Buckberg GD, Ignarro LJ, Beyersdorf F: Reduction of reoxygenation injury and nitric oxide production in the cyanotic immature heart by controlling PO2. Eur J Cardiothorac Surg 1995;9:410–418.
32.
Fisher AB, Dodia C, Tan ZT, Ayene I, Eckenhoff RG: Oxygen-dependent lipid peroxidation during lung ischemia. J Clin Invest 1991;88:674–679.
1999
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.