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Roles of iNOS and nNOS in sepsis-induced pulmonary apoptosis

Jill C Rudkowski1, Esther Barreiro, Rania Harfouche

  • 1Rm. L3.03, Critical Care Division, Royal Victoria Hospital, 687 Pine Ave. West, Montreal, H3A 1A1 Quebec, Canada.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|December 9, 2003
PubMed

Insights

Nitric oxide (NO) from inducible NO synthase (iNOS) protects lung cells from apoptosis during sepsis. Inhibiting iNOS worsens sepsis-induced lung injury, highlighting iNOS

Area of Science:

  • Pulmonary Medicine
  • Cellular Biology
  • Immunology

Background:

  • Sepsis-induced acute lung injury involves programmed cell death (apoptosis) in pulmonary cells.
  • Nitric oxide (NO) modulates apoptosis, but the role of inducible NO synthase (iNOS)-derived NO in sepsis-related lung apoptosis is unclear.

Purpose of the Study:

  • To investigate the functional role of iNOS-derived NO in sepsis-induced pulmonary apoptosis.

Main Methods:

  • A rat model of Escherichia coli lipopolysaccharide (LPS)-induced sepsis was used.
  • Apoptosis was assessed via DNA fragmentation, TUNL staining, and caspase activation.
  • Experiments were conducted with and without a selective iNOS inhibitor (1400W) and in iNOS knockout mice.

Main Results:

  • LPS administration increased pulmonary apoptosis and caspase-3 activity.
  • Inhibition of iNOS with 1400W exacerbated LPS-induced apoptosis and caspase activation.
  • iNOS knockout mice exhibited increased pulmonary apoptosis compared to wild-type mice, both basally and after LPS challenge.

Conclusions:

  • NO derived from iNOS plays a significant protective role against sepsis-induced pulmonary apoptosis.
  • Targeting iNOS may be a therapeutic strategy for managing sepsis-induced lung injury.

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