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Inhibition of neuronal nitric oxide synthase activity does not alter vasopressin secretion in septic rats

Abstract

Background/Purpose

During the early phase of sepsis, hypotension is accompanied by increase of plasma vasopressin hormone (AVP) levels, which decline during the late phase. This hypotension is due in part to increase of nitric oxide (NO) synthesis by nitric oxide synthase (NOS) enzyme. Neuronal isoform of this enzyme (nNOS) is present in vasopressinergics neurons of hypothalamus, but its role in vasopressin secretion during sepsis is unknown.

Methods

We evaluated the role of nNOS in NO production and vasopressin secretion during sepsis. Wistar rats received 7-nitroindazole (50 mg/kg, i.p.), an inhibitor of nNOS activity, or vehicle and were submitted to septic stimulus by cecal ligation and puncture (CLP). At the time points 0, 4, 6, 18 and 24 h after sepsis induction the animals were decapitated and neurohypophysis and hypothalamus were removed for analysis of vasopressin content and NOS activity, respectively. Hematocrit, serum sodium, osmolality, proteins and plasmatic AVP were quantified.

Results

Mortality was not affected by 7-nitroindazole (7-NI). Sodium and plasma proteins levels decreased after CLP and the treatment anticipated the protein loss, and delayed serum sodium decrease. Septic animals treated with 7-NI showed decrease of osmolality 4 h after CLP. Nitric oxide synthase activity in hypothalamus increased at 4 and 24 h after CLP and was reduced with 7-NI. Neurohypophysis content of AVP diminished after CLP and 7-NI did not alter this parameter. Plasma AVP levels increased at 6 h and decreased 18 and 24 h after CLP. Treatment with 7-NI did not alter plasma vasopressin levels.

Conclusion

We concluded that nNOS does not have a substantial role in vasopressin secretion during experimental sepsis.

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Acknowledgements

The authors thank Nadir M. Fernandes, Fabyola Mestriner e Milene Mantovani for the excellent technical assistance. José Antunes-Rodrigues and Lucila L. K. Elias provided the infrastructure for the RIA analyses. Financial support from CNPq and CAPES is gratefully acknowledged.

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Correspondence to Camila Henriques Coelho.

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All procedures were done following the Ethics Committee of Animal Experimentation at the University of São Paulo (CEUA)-Campus Ribeirão Preto.

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Coelho, C.H., Martins, T.F., Oliveira-Pelegrin, G.R. et al. Inhibition of neuronal nitric oxide synthase activity does not alter vasopressin secretion in septic rats. Pituitary 20, 333–339 (2017). https://doi.org/10.1007/s11102-017-0786-x

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  • DOI: https://doi.org/10.1007/s11102-017-0786-x

Keywords

  • CLP
  • Neuronal NOS
  • Nitric oxide
  • Polymicrobial sepsis
  • Vasopressin