Endogenous nitric oxide as a probable modulator of pulmonary circulation and hypoxic pressor response in vivo

M. G. Persson, L. E. Gustafsson, N. P. Wiklund, S. Moncada, P. Hedqvist

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191 Scopus citations

Abstract

The objective of this study was to investigate the role of endogenous nitric oxide, formed from L-arginine, in the regulation of pulmonary circulation in vivo, with special reference to the hypoxic pressor response. In artificially ventilated open-chest rabbits, pulmonary vascular resistance at normoxic ventilation (F(IO2) = 21%) was 78 ± 16 cmH2O ml-1 min 1000-1 (mRU(L)). Hypoxic ventilation (F(IO2) = 10%) increased pulmonary vascular resistance to 117 ± 17 mRU(L). N(ω)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased pulmonary vascular resistance at normoxic ventilation to 192 ± 28 mRU(L) and during hypoxic ventilation to 462 ± 80 mRU(L). During N(ω)-nitro-L-arginine methylester infusion there was also an increase in mean arterial blood pressure as well as a decrease in cardiac output that was even more pronounced during hypoxic ventilation. L-arginine reversed the effect of N(ω)-nitro-L-arginine methylester on pulmonary vascular resistance at normoxic ventilation to 140 ± 26 mRU(L) and at hypoxic ventilation to 239 ± 42 mRU(L). In spontaneously breathing closed-chest rabbits, N(ω)-nitro-L-arginine methylester evoked a marked decrease in arterial P(O2) and increases in respiration frequency and central venous pressure, while blood pH, P(CO2) and base excess remained unchanged. Taken together these findings indicate that endogenous nitric oxide, formed from L-arginine, might be a regulator of ventilation-perfusion matching at normoxic ventilation, and that nitric oxide acts as an endogenous modulator of the hypoxic pressor response.

Original languageEnglish
Pages (from-to)449-457
Number of pages9
JournalActa Physiologica Scandinavica
Volume140
Issue number4
DOIs
StatePublished - 1990
Externally publishedYes

Keywords

  • EDRF
  • arginine analogues
  • endothelium-derived relaxing factor
  • hypoxia
  • hypoxic pressor response
  • nitric oxide
  • pulmonary circulation
  • vasoconstriction

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