Role of nitric oxide synthase types II and III in early protection against endotoxin-induced lung injury: DISCUSSION (part 1)

DISCUSSION (part 1)

Knowing the dosage of LPS and the mode of its administration (intraperitonial, intravenous, injection, infusion) is essential when studying the role of nitric oxide in endotoxe-mia. Some authorities in the field consider an initial fall in blood pressure occurring some minutes after administration of LPS to be an epiphenomenon – its mechanism not worthy of study. This reasoning seems correct when directly transferring experimental results to a clinical situation; however, the data on immediate response to endotoxin may provide valuable information about the mechanisms of mortality during septic shock. In the present study, we decided to infuse Sprague-Dawley rats with LPS (2 mg/kg/min intravenously for 10 mins). This procedure produces two distinct phases of arterial hypotension – an early phase (most profoundly marked during the initial 15 to 30 mins) and a late phase, which is lethal 5 to 6 h after the administration of endotoxin.
This model allowed for discrimination between early and late effects of NOS inhibition during sepsis. A nonselective NOS inhibitor (L-NNA) (10 mg/kg intravenously) injected 45 mins before LPS infusion resulted in sudden death of rats (less than 25 mins, L-NNA plus LPS group) (Figure 2) accompanied by macroscopically and microscopically diagnosed symptoms similar to those of acute respiratory distress syndrome. To prove that lack of endogenous nitric oxide was responsible for the sudden death of animals after LPS infusion, the nitric oxide-donor SNAP (L-NNA plus SNAP plus LPS group) (Figure 2) was used as a source of exogenous nitric oxide, and, indeed, it completely restored early mortality caused by L-NNA given before LPS infusion.

This entry was posted in Lung injury and tagged 1-Amino-2-hydroxy-guanidine, Endotoxic shock, NG-nitro-L-arginine, Nitric oxide, Nitric oxide synthase type II, Nitric oxide synthase type III, S-nitroso-N-acetyl-penicillamine.