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Nitric oxide synthase 2-derived NO in endotoxemia is not sufficient to cause hemodynamic effects
Critical Care volume 12, Article number: P392 (2008)
Inducible nitric oxide synthase (NOS2)-derived NO is considered a central mediator of the cardiovascular collapse in endotoxemia and sepsis. Nevertheless, NOS2 mice display enhanced morbidity and mortality after administration of endotoxin or TNF. This is probably due to the documented indispensable antioxidant and anti-inflammatory properties of NO [1, 2].
We used TLR4-/- mice (natural mutants and induced mutants) and control mice, lipopolysaccharide (LPS) from Sigma and Invivogen, measured NOx using Griess reagents, followed the blood pressure using tail cuff techniques, performed immunohistochemistry and monitored lethality and body temperature.
We observed in TLR4-/- mice resistant to the inflammatory and lethal effects of endotoxin that various LPS preparations obtained from Sigma – but not Invivogen – were able to induce as much NOS2 and NOx as control mice but without resulting in hemodynamic effects, measured as changes in blood pressure. This is dependent on non-LPS bacterial products in this preparation. These contaminants do not induce cytokine production nor cause suffering. Further immunohistochemical investigations showed that NOS2 was induced in a similar way in TLR4-/- mice as previously described in wildtype mice , namely predominantly in the liver and gut. In addition, dose–response experiments showed that the amount of NOx produced in wildtype mice was similar after low doses of LPS to that after lethal doses of LPS.
We conclude that NOS2-derived NO is not sufficient to cause hemodynamic effects and that the cardiovascular collapse is dependent on an extra stimulus.
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Brouckaert, P., Bultinck, J., Rogge, E. et al. Nitric oxide synthase 2-derived NO in endotoxemia is not sufficient to cause hemodynamic effects. Crit Care 12, P392 (2008). https://doi.org/10.1186/cc6613
- Nitric Oxide
- Control Mouse
- Bacterial Product
- Hemodynamic Effect
- Griess Reagent