Skip to main content

Endothelial nitric oxide synthase deficiency and inducible nitric oxide synthase inhibition in the setting of septic cardiomyopathy


Nitric oxide (NO) plays a central role in the pathogenesis of septic cardiomyopathy. However, the relative contribution of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) remains unclear. The aim of this study is to elucidate the influence of eNOS and iNOS on cardiac function, NO production rate and survival in the clinically relevant polymicrobial cecum ligation and puncture (CLP) model of sepsis.


B6/c57 wildtype (WT) and eNOS-/- mice were rendered septic by CLP or were sham operated. Immediately, the selective iNOS inhibitor 1400 W (6.6 mg/kg body weight intraperitoneally and subcutaneously) or carrier were applied. At 12 hours after sepsis induction, heart function was assessed by pressure–volume loops (1.4 Fr Millar catheter). NOx levels and endogenous NO production (blood plasma/heart tissue) were measured via gas-phase chemiluminescence detection, high-performance liquid chromatography and electron paramagnetic resonance spectroscopy. To evaluate apoptosis and inflammation, quantitative immunochemistry was applied. iNOS expression was analyzed via RT-PCR.


Cardiac function was significantly impaired solely in septic WT mice with diminished left ventricular developed pressure/dP d tmax(dP dtmax: WT CLP = 10,981 ± 1,100 mmHg/s vs. WT sham = 13,408 ± 827 mmHg/s; P < 0.01) and increased left-ventricular volumes. Inhibition of iNOS in septic WT mice resulted in ameliorated cardiovascular impairment, whereas no signs of septic cardiomyopathy were observed in septic eNOS-/-. In contrast to septic eNOS-/- mice, septic WT mice developed a significant increase in NO3-, NO2- and bioactive NO levels. eNOS deficiency was associated with diminished apoptosis and modified inflammation. In eNOS-/- mice, a decreased iNOS expression was observed compared with septic WT mice. Both genetic eNOS deficiency and pharmacologic iNOS inhibition was associated with a significant survival benefit. While eNOS-/- mice survived longest, additional iNOS inhibition in the latter diminished this benefit significantly.


In this clinically relevant model of sepsis, eNOS constitutes an important factor mediating septic cardiomyopathy. To what extent the diminished inflammation, apoptosis, NO production rate, iNOS expression and prolonged survival in eNOS-/- mice contribute to the observed benefits remains to be clarified in future studies.

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sandt, A.V.d., Windler, R., Gödecke, A. et al. Endothelial nitric oxide synthase deficiency and inducible nitric oxide synthase inhibition in the setting of septic cardiomyopathy. Crit Care 13 (Suppl 1), P164 (2009).

Download citation

  • Published:

  • DOI:


  • Nitric Oxide
  • iNOS Expression
  • iNOS Inhibition
  • Sepsis Induction
  • Septic Cardiomyopathy