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. 1996 May;118(1):179–185. doi: 10.1111/j.1476-5381.1996.tb15383.x

Nitric oxide synthase-cyclo-oxygenase pathways in organum vasculosum laminae terminalis: possible role in pyrogenic fever in rabbits.

J H Lin 1, M T Lin 1
PMCID: PMC1909491  PMID: 8733593

Abstract

1. Fever was induced in rabbits by administration of Escherichia coli endotoxin (lipopolysaccharide; LPS; 0.001-10 micrograms) into the organum vasculosum laminae terminalis (OVLT). Deep body temperature was evaluated over a period of 7 h. 2. The LPS-induced febrile response was mimicked by intra-OVLT injection of the nitric oxide (NO) donors, S-nitroso-acetylpenicillamine (SNAP, 1-10 micrograms), sodium nitroprusside (SNP, 50 micrograms), or hydroxylamine (10 micrograms), the cyclic GMP analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP, 10-100 micrograms), or prostaglandin E2 (PGE2, 0.2 micrograms). 3. Dexamethasone (Dex, a potent inhibitor of the transcription of inducible NO synthase, iNOS, 10 micrograms), anisomycin (a protein synthesis inhibitor, 100 micrograms), L-N5-(1-iminoethyl)ornithine (L-NIO; an irreversible NOS inhibitor, 10-200 micrograms), aminoguanidine (a specific iNOS inhibitor, 1000 micrograms), or NG-methyl-L-arginine acetate (L-NMMA, a NOS inhibitor, 100 micrograms) inhibited fever induced by LPS when injected into the OVLT 1 h before LPS injection. An intra-OVLT dose of 1000 micrograms of NG-nitro-L-arginine methyl ester (L-NAME, a potent inhibitor of constitutive NOS) did not exhibit antipyretic effects. 4. Methylene blue (an inhibitor of NOS and soluble guanylate cyclase, 1-10 micrograms), 6-(phenylamino)-5,8-quinolinedione (LY-83583; an inhibitor of soluble guanylate cyclase and NO release, 20 micrograms), or indomethacin (an inhibitor of cyclo-oxygenase, COX, 400 micrograms) inhibited fever induced by LPS when injected into the OVLT 1 h before LPS injection. Pretreatment with methylene blue or haemoglobin (a NO scavenger, 100 micrograms) attenuated the fever induced by intra-OVLT injection of SNAP. 5. The PGE2-induced fever was potentiated, rather then attenuated, by pretreatment with an intra-OVLT dose of animoguanidine (1000 micrograms), L-NMMA (100 micrograms) or L-NIO (200 micrograms). 6. These results suggest that iNOS-COX pathways in the OVLT represent an important mechanism for modulation of pyrogenic fever in rabbits.

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Selected References

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  1. Akarasereenont P., Mitchell J. A., Appleton I., Thiemermann C., Vane J. R. Involvement of tyrosine kinase in the induction of cyclo-oxygenase and nitric oxide synthase by endotoxin in cultured cells. Br J Pharmacol. 1994 Dec;113(4):1522–1528. doi: 10.1111/j.1476-5381.1994.tb17169.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blatteis C. M., Bealer S. L., Hunter W. S., Llanos-Q J., Ahokas R. A., Mashburn T. A., Jr Suppression of fever after lesions of the anteroventral third ventricle in guinea pigs. Brain Res Bull. 1983 Nov;11(5):519–526. doi: 10.1016/0361-9230(83)90124-7. [DOI] [PubMed] [Google Scholar]
  3. Bredt D. S., Snyder S. H. Nitric oxide, a novel neuronal messenger. Neuron. 1992 Jan;8(1):3–11. doi: 10.1016/0896-6273(92)90104-l. [DOI] [PubMed] [Google Scholar]
  4. Canteros G., Rettori V., Franchi A., Genaro A., Cebral E., Faletti A., Gimeno M., McCann S. M. Ethanol inhibits luteinizing hormone-releasing hormone (LHRH) secretion by blocking the response of LHRH neuronal terminals to nitric oxide. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3416–3420. doi: 10.1073/pnas.92.8.3416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Corbett J. A., Tilton R. G., Chang K., Hasan K. S., Ido Y., Wang J. L., Sweetland M. A., Lancaster J. R., Jr, Williamson J. R., McDaniel M. L. Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes. 1992 Apr;41(4):552–556. doi: 10.2337/diab.41.4.552. [DOI] [PubMed] [Google Scholar]
  6. Cranston W. I., Duff G. W., Hellon R. F., Mitchell D., Townsend Y. Evidence that brain prostaglandin synthesis is not essential in fever. J Physiol. 1976 Jul;259(1):239–249. doi: 10.1113/jphysiol.1976.sp011464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fu J. Y., Masferrer J. L., Seibert K., Raz A., Needleman P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem. 1990 Oct 5;265(28):16737–16740. [PubMed] [Google Scholar]
  8. Hashimoto M., Ueno T., Iriki M. What roles does the organum vasculosum laminae terminalis play in fever in rabbits? Pflugers Arch. 1994 Nov;429(1):50–57. doi: 10.1007/BF02584029. [DOI] [PubMed] [Google Scholar]
  9. Hemler M., Lands W. E. Purification of the cyclooxygenase that forms prostaglandins. Demonstration of two forms of iron in the holoenzyme. J Biol Chem. 1976 Sep 25;251(18):5575–5579. [PubMed] [Google Scholar]
  10. Hess D. T., Lin L. H., Freeman J. A., Norden J. J. Modification of cysteine residues within G(o) and other neuronal proteins by exposure to nitric oxide. Neuropharmacology. 1994 Nov;33(11):1283–1292. doi: 10.1016/0028-3908(94)90028-0. [DOI] [PubMed] [Google Scholar]
  11. Ignarro L. J., Ballot B., Wood K. S. Regulation of soluble guanylate cyclase activity by porphyrins and metalloporphyrins. J Biol Chem. 1984 May 25;259(10):6201–6207. [PubMed] [Google Scholar]
  12. Ignarro L. J. Signal transduction mechanisms involving nitric oxide. Biochem Pharmacol. 1991 Feb 15;41(4):485–490. doi: 10.1016/0006-2952(91)90618-f. [DOI] [PubMed] [Google Scholar]
  13. Kalyanaraman B., Mason R. P., Tainer B., Eling T. E. The free radical formed during the hydroperoxide-mediated deactivation of ram seminal vesicles is hemoprotein-derived. J Biol Chem. 1982 May 10;257(9):4764–4768. [PubMed] [Google Scholar]
  14. Kanner J., Harel S., Granit R. Nitric oxide, an inhibitor of lipid oxidation by lipoxygenase, cyclooxygenase and hemoglobin. Lipids. 1992 Jan;27(1):46–49. doi: 10.1007/BF02537058. [DOI] [PubMed] [Google Scholar]
  15. Kapás L., Shibata M., Kimura M., Krueger J. M. Inhibition of nitric oxide synthesis suppresses sleep in rabbits. Am J Physiol. 1994 Jan;266(1 Pt 2):R151–R157. doi: 10.1152/ajpregu.1994.266.1.R151. [DOI] [PubMed] [Google Scholar]
  16. Lee S. H., Soyoola E., Chanmugam P., Hart S., Sun W., Zhong H., Liou S., Simmons D., Hwang D. Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem. 1992 Dec 25;267(36):25934–25938. [PubMed] [Google Scholar]
  17. Lowenstein C. J., Glatt C. S., Bredt D. S., Snyder S. H. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6711–6715. doi: 10.1073/pnas.89.15.6711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lyons C. R., Orloff G. J., Cunningham J. M. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. J Biol Chem. 1992 Mar 25;267(9):6370–6374. [PubMed] [Google Scholar]
  19. Maier J. A., Hla T., Maciag T. Cyclooxygenase is an immediate-early gene induced by interleukin-1 in human endothelial cells. J Biol Chem. 1990 Jul 5;265(19):10805–10808. [PubMed] [Google Scholar]
  20. Masferrer J. L., Seibert K., Zweifel B., Needleman P. Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3917–3921. doi: 10.1073/pnas.89.9.3917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Matsuda T., Hori T., Nakashima T. Thermal and PGE2 sensitivity of the organum vasculosum lamina terminalis region and preoptic area in rat brain slices. J Physiol. 1992 Aug;454:197–212. doi: 10.1113/jphysiol.1992.sp019260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matsumura K., Watanabe Y., Onoe H., Watanabe Y., Hayaishi O. High density of prostaglandin E2 binding sites in the anterior wall of the 3rd ventricle: a possible site of its hyperthermic action. Brain Res. 1990 Nov 12;533(1):147–151. doi: 10.1016/0006-8993(90)91808-t. [DOI] [PubMed] [Google Scholar]
  23. Mayer B., Brunner F., Schmidt K. Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol. 1993 Jan 26;45(2):367–374. doi: 10.1016/0006-2952(93)90072-5. [DOI] [PubMed] [Google Scholar]
  24. McCall T. B., Feelisch M., Palmer R. M., Moncada S. Identification of N-iminoethyl-L-ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells. Br J Pharmacol. 1991 Jan;102(1):234–238. doi: 10.1111/j.1476-5381.1991.tb12159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mellion B. T., Ignarro L. J., Ohlstein E. H., Pontecorvo E. G., Hyman A. L., Kadowitz P. J. Evidence for the inhibitory role of guanosine 3', 5'-monophosphate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators. Blood. 1981 May;57(5):946–955. [PubMed] [Google Scholar]
  26. Milton A. S., Wendlandt S. A possible role for prostaglandin E1 as a modulator for temperature regulation in the central nervous system of the cat. J Physiol. 1970 Apr;207(2):76P–77P. [PubMed] [Google Scholar]
  27. Minc-Golomb D., Tsarfaty I., Schwartz J. P. Expression of inducible nitric oxide synthase by neurones following exposure to endotoxin and cytokine. Br J Pharmacol. 1994 Jul;112(3):720–722. doi: 10.1111/j.1476-5381.1994.tb13136.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Misko T. P., Moore W. M., Kasten T. P., Nickols G. A., Corbett J. A., Tilton R. G., McDaniel M. L., Williamson J. R., Currie M. G. Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur J Pharmacol. 1993 Mar 16;233(1):119–125. doi: 10.1016/0014-2999(93)90357-n. [DOI] [PubMed] [Google Scholar]
  29. Mitchell J. A., Akarasereenont P., Thiemermann C., Flower R. J., Vane J. R. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693–11697. doi: 10.1073/pnas.90.24.11693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  31. Mülsch A., Busse R., Liebau S., Förstermann U. LY 83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase. J Pharmacol Exp Ther. 1988 Oct;247(1):283–288. [PubMed] [Google Scholar]
  32. Nakamori T., Morimoto A., Yamaguchi K., Watanabe T., Murakami N. Interleukin-1 beta production in the rabbit brain during endotoxin-induced fever. J Physiol. 1994 Apr 1;476(1):177–186. [PMC free article] [PubMed] [Google Scholar]
  33. Rees D. D., Cellek S., Palmer R. M., Moncada S. Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: an insight into endotoxin shock. Biochem Biophys Res Commun. 1990 Dec 14;173(2):541–547. doi: 10.1016/s0006-291x(05)80068-3. [DOI] [PubMed] [Google Scholar]
  34. Reimers J. I., Bjerre U., Mandrup-Poulsen T., Nerup J. Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases. Cytokine. 1994 Sep;6(5):512–520. doi: 10.1016/1043-4666(94)90079-5. [DOI] [PubMed] [Google Scholar]
  35. SAWYER C. H., EVERETT J. W., GREEN J. D. The rabbit diencephalon in stereotaxic coordinates. J Comp Neurol. 1954 Dec;101(3):801–824. doi: 10.1002/cne.901010307. [DOI] [PubMed] [Google Scholar]
  36. Salvemini D., Korbut R., Anggård E., Vane J. Immediate release of a nitric oxide-like factor from bovine aortic endothelial cells by Escherichia coli lipopolysaccharide. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2593–2597. doi: 10.1073/pnas.87.7.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Salvemini D., Misko T. P., Masferrer J. L., Seibert K., Currie M. G., Needleman P. Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7240–7244. doi: 10.1073/pnas.90.15.7240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Salvemini D., Settle S. L., Masferrer J. L., Seibert K., Currie M. G., Needleman P. Regulation of prostaglandin production by nitric oxide; an in vivo analysis. Br J Pharmacol. 1995 Mar;114(6):1171–1178. doi: 10.1111/j.1476-5381.1995.tb13330.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sautebin L., Ialenti A., Ianaro A., Di Rosa M. Modulation by nitric oxide of prostaglandin biosynthesis in the rat. Br J Pharmacol. 1995 Jan;114(2):323–328. doi: 10.1111/j.1476-5381.1995.tb13230.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schmidt M. J., Sawyer B. D., Truex L. L., Marshall W. S., Fleisch J. H. LY83583: an agent that lowers intracellular levels of cyclic guanosine 3',5'-monophosphate. J Pharmacol Exp Ther. 1985 Mar;232(3):764–769. [PubMed] [Google Scholar]
  41. Schwaner I., Offermanns S., Spicher K., Seifert R., Schultz G. Differential activation of Gi and Gs proteins by E- and I-type prostaglandins in membranes from the human erythroleukaemia cell line, HEL. Biochim Biophys Acta. 1995 Feb 16;1265(1):8–14. doi: 10.1016/0167-4889(94)00198-n. [DOI] [PubMed] [Google Scholar]
  42. Simmons M. L., Murphy S. Cytokines regulate L-arginine-dependent cyclic GMP production in rat glial cells. Eur J Neurosci. 1993 Jul 1;5(7):825–831. doi: 10.1111/j.1460-9568.1993.tb00934.x. [DOI] [PubMed] [Google Scholar]
  43. Stadler J., Stefanovic-Racic M., Billiar T. R., Curran R. D., McIntyre L. A., Georgescu H. I., Simmons R. L., Evans C. H. Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. J Immunol. 1991 Dec 1;147(11):3915–3920. [PubMed] [Google Scholar]
  44. Stitt J. T. Differential sensitivity in the sites of fever production by prostaglandin E1 within the hypothalamus of the rat. J Physiol. 1991 Jan;432:99–110. doi: 10.1113/jphysiol.1991.sp018378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stitt J. T. Evidence for the involvement of the organum vasculosum laminae terminalis in the febrile response of rabbits and rats. J Physiol. 1985 Nov;368:501–511. doi: 10.1113/jphysiol.1985.sp015872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Swierkosz T. A., Mitchell J. A., Warner T. D., Botting R. M., Vane J. R. Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids. Br J Pharmacol. 1995 Apr;114(7):1335–1342. doi: 10.1111/j.1476-5381.1995.tb13353.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Szabó C., Thiemermann C., Wu C. C., Perretti M., Vane J. R. Attenuation of the induction of nitric oxide synthase by endogenous glucocorticoids accounts for endotoxin tolerance in vivo. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):271–275. doi: 10.1073/pnas.91.1.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Won S. J., Lin M. T. Pyrogenicity of interferon and its inducer in rabbits. Am J Physiol. 1988 Mar;254(3 Pt 2):R499–R507. doi: 10.1152/ajpregu.1988.254.3.R499. [DOI] [PubMed] [Google Scholar]
  49. Won S. J., Lin M. T. Pyrogenicity of polyadenylic.polyuridylic acid in rabbits. Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):551–557. doi: 10.1007/BF00169561. [DOI] [PubMed] [Google Scholar]
  50. Wu C. C., Croxtall J. D., Perretti M., Bryant C. E., Thiemermann C., Flower R. J., Vane J. R. Lipocortin 1 mediates the inhibition by dexamethasone of the induction by endotoxin of nitric oxide synthase in the rat. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3473–3477. doi: 10.1073/pnas.92.8.3473. [DOI] [PMC free article] [PubMed] [Google Scholar]

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