Skip to main content

Advertisement

Log in

Role of nitric oxide in thermoregulation during septic shock: involvement of vasopressin

  • Exercise, Temperature Regulation
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

We tested the hypothesis that the nitric oxide (NO) pathway in the central nervous system (CNS) plays a role in hypothermia, as well as in the febrile response during experimental septic shock, by regulating vasopressin (AVP) release. Experiments were performed on male Wistar rats treated with N G-nitro-l-arginine methyl ester (l-NAME), a non-selective NO synthase (NOS) inhibitor, injected intracerebroventricularly (250 µg/1 μl) 30 min before lipopolysaccharide (LPS) 1.5 mg/kg i.v. injection. One hour after LPS administration we observed a significant drop in body temperature (hypothermic response), followed by a temperature increase after the second hour (febrile response), which remained until the end of the experiment. Increased plasmatic AVP levels were concomitantly observed during hypothermia, nearly returning to basal levels during the febrile phase. When l-NAME was administered with LPS, plasmatic AVP concentrations remained high throughout the experiment, hypothermia was accentuated and the febrile response was abolished. Additionally, pre-treatment with β-mercapto-β,β-cyclopentamethylenepropionyl1, O-Et-Tyr2, Val4, Arg8-vasopressin, an AVP V1 receptor blocker (10 µg/kg) administered i.v., reduced hypothermia and exacerbated the febrile response to endotoxin. In conclusion, our data indicate that the central NO pathway plays an inhibitory role in AVP release during experimental septic shock, which seems to be critical for the thermoregulation during this pathophysiological state.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A–C. A
Fig. 2.
Fig. 3A–C. A

Similar content being viewed by others

References

  1. Aiura K, Ueda M, Endo M (1995) Circulating concentrations and physiological role of atrial natriuretic peptide during endotoxic shock in the rat. Crit Care Med 23:1898–1906

    Google Scholar 

  2. Almeida MC, Carnio EC, Branco LG (1999) Role of nitric oxide in hypoxia inhibition of fever. J Appl Physiol 87:2186–2190

    Google Scholar 

  3. Ataoglu H, Dogan MD, Mustafa F, Akarsu ES (2000) Candida albicans and Saccharomyces cerevisiae cell wall mannans produce fever in rats: role of nitric oxide and cytokines. Life Sci 67:2247–2256

    Article  CAS  PubMed  Google Scholar 

  4. Chen X, Landgraf R, Pittman QJ (1997) Differential ventral septal vasopressin release is associated with sexual dimorphism in PGE2 fever. Am J Physiol 272:R1664–R1669

    CAS  PubMed  Google Scholar 

  5. Cooper KE, Naylor AM, Veale WL (1987) Evidence supporting a role for endogenous vasopressin in fever suppression in the rat. J Physiol (Lond) 387:163–172

    Google Scholar 

  6. Derijk RH, Berkenbosh F (1994) Hypothermia to endotoxin involves the cytokine tumor necrosis and the neuropeptide vasopressin in rats. Am J Physiol 266:R9–R14

    CAS  Google Scholar 

  7. Ermish A (1992) Peptide receptors of the blood-brain barrier and substrate transport into the brain. Prog Brain Res 91:155–161

    PubMed  Google Scholar 

  8. Giusti-Paiva A, de Castro M, Antunes-Rodrigues J, Carnio EC (2002) Inducible nitric oxide synthase pathway in the central nervous system and vasopressin release during experimental septic shock. Crit Care Med 30:1306–1310

    Google Scholar 

  9. Gourine AV (1995) Pharmacological evidence that nitric oxide can act as an endogenous antipyretic factor in endotoxin-induced fever in rabbits. Gen Pharmacol 26:835–841

    Article  CAS  Google Scholar 

  10. Harris RL, Musher DM, Bloom K, Gathe J, Rice L, Sugarmann B, Williams Jr TW, Young EJ (1987) Manifestation of sepsis. Arch Intern Med 147:1895–1906

    CAS  PubMed  Google Scholar 

  11. Itoh S (1980) Effect of vasopressin on lipid metabolism. In: Integrative mechanism of neuroendocrine system. Sapporo, Japan, pp 175–197

  12. Kamerman P, Fuller A (2000) Effects of nitric oxide synthase inhibitors on the febrile response to lipopolysaccharide and muramyl dipeptide in guinea pigs. Life Sci 67:2639–2645

    CAS  PubMed  Google Scholar 

  13. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142

    CAS  PubMed  Google Scholar 

  14. Morrison DC, Ryan JL (1987) Endotoxin and disease mechanisms. Annu Rev Med 38:417–432

    CAS  PubMed  Google Scholar 

  15. Nathan C, Xie QW (1994) Regulation of biosynthesis of nitric oxide. J Biol Chem 269:13725–13728

    CAS  PubMed  Google Scholar 

  16. Naylor AM, Pittman QJ, Veale WL (1988) Stimulation of vasopressin release in the ventral septum of the rat brain suppresses prostaglandin E1 fever. J Physiol (Lond) 399:177–189

    Google Scholar 

  17. Okuno A, Yamamoto M, Itoh S (1965) Lowering of the body temperature induced by vasopressin. Jpn J Physiol 15:378–387

    CAS  Google Scholar 

  18. Ota M, Crofton JT, Festavan GT (1993) Evidence that nitric oxide can act centrally to stimulate vasopressin release. Neuroendocrinology 57:955–959

    CAS  PubMed  Google Scholar 

  19. Pardridge WM (1983) Neuropeptides and blood-brain barrier. Annu Rev Physiol 45:73–82

    Article  CAS  PubMed  Google Scholar 

  20. Paro FM, Almeida MC, Carnio EC, Branco LGS (2003) Role of L-glutamate in systemic AVP-induced hypothermia. J Appl Physiol 94:271–277

    Google Scholar 

  21. Parrillo JE, Parker MM, Natanson C (1990) Septic shock in humans: advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 113:227–242

    CAS  PubMed  Google Scholar 

  22. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, San Diego

  23. Reimmers JI, Bjerre U, Mandrup-Poulsen T, Nerup J (1994) Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases. Cytokine 6:512–520

    PubMed  Google Scholar 

  24. Rietschel ET, Brade H, Holst O, Brade L, Muller LS, Mamat LS, Zahringer U, Beckmann F, Seydel U, Bradenburg K (1996) Bacterial endotoxin: chemical constitution, biological recognition, host response, and immunological detoxification. Curr Top Microbiol Immunol 216:39–81

    CAS  PubMed  Google Scholar 

  25. Romanovsky AA, Shido O, Sakurada S, Sugimoto N, Nagasaka T (1996) Endotoxin shock: thermoregulatory mechanisms. Am J Physiol 270:R693–R703

    CAS  Google Scholar 

  26. Romanovsky AA, Shido O, Sakurada S, Sugimoto N, Nagasaka T (1997) Endotoxin shock-associated hypothermia. How and why does it occur? Ann N Y Acad Sci 813:733–737

    CAS  PubMed  Google Scholar 

  27. Roth J, Storr B, Goldbach JM, Voigt K, Zeisberger E (1999) Dose-dependent attenuation of lipopolysaccharide-fever by inhibitors of inducible nitric oxide-synthase in guinea pigs. Eur J Pharmacol 383:177–187

    CAS  PubMed  Google Scholar 

  28. Scammell TE, Elmquist JK, Saper CB (1996) Inhibition of nitric oxide synthase produces hypothermia and depress lipoplysaccharide fever. Am J Physiol 40:R333–R338

    Google Scholar 

  29. Shido O, Kifune A, Nagasaka T (1984) Baroreflexive suppression of heat production and fall in body temperature following peripheral administration of vasopressin in rats. Jpn J Physiol 34:397–406

    CAS  PubMed  Google Scholar 

  30. Steiner AA, Branco LGS (2001) Nitric oxide in the regulation of body temperature and fever. J Therm Biol 26:325–330

    Article  CAS  Google Scholar 

  31. Steiner AA, Carnio EC, Antunes-Rodrigues J, Branco LGS (1998) Role of nitric oxide in systemic vasopressin-induced hypothermia. Am J Physiol 275:R937–R941

    CAS  PubMed  Google Scholar 

  32. Steiner AA, Carnio EC, Antunes-Rodrigues J, Branco LGS (1999) Endogenous vasopressin does not mediate hypoxia-induced anapyrexia in rats. J Appl Physiol 86:469–473

    CAS  PubMed  Google Scholar 

  33. Uribe RM, Lee S, Rivier C (1999) Endotoxin stimulates nitric oxide production in the paraventricular nucleus of the hypothalamus through nitric oxide synthase I: Correlation with hypothalamic-pituitary-adrenal axis activation. Endocrinology 140:5971–5981

    CAS  Google Scholar 

  34. Wilson MF, Brackett DJ, Hinshaw LB (1981) Vasopressin release during sepsis and septic shock in baboons and dogs. Surg Gynecol Obstet 153:869–872

    CAS  PubMed  Google Scholar 

  35. Yasin S, Costa A, Trainer P, Windle R, Forsting ML, Grossman A (1993) Nitric oxide modulates the release of vasopressin from rat hypothalamic explants, Endocrinology 133:1466–1469

    Google Scholar 

Download references

Acknowledgements

We would like to thank Leila M.M. Alves and Flávia F. Salata for the excellent technical assistance. This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Fundação de Amparo ao Ensino e à Pesquisa do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (FAEPA), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and PRONEX.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Evelin C. Carnio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giusti-Paiva, A., Branco, L.G.S., de Castro, M. et al. Role of nitric oxide in thermoregulation during septic shock: involvement of vasopressin. Pflugers Arch - Eur J Physiol 447, 175–180 (2003). https://doi.org/10.1007/s00424-003-1164-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-003-1164-2

Keywords

Navigation