Role of nitric oxide synthase types II and III in early protection against endotoxin-induced lung injury: DISCUSSION (part 4)

RT-PCR technique was used to reveal the kinetics of NOS-II mRNA appearance in the lung. The 384 base pair single band was amplified from samples with NOS-II primers only 30 and 120 mins after LPS infusion, but not in controls or in rat pulmonary tissue treated for 15 mins and 25 mins (data not shown) with LPS . These data, together with results from dot blot analysis, suggest that NOS-II transcripts appeared in endotoxemic rat lung not earlier than 30 mins after LPS infusion. Accordingly, we conclude that in the early phase of endotoxemia, LPS released nitric oxide by activation of NOS-III but not NOS-II.This conclusion provides strong support for LPS pneumotoxicity in blood-perfused isolated rat lung. In such preparation, LPS at a concentration of 300 |ig/mL caused negligible impairment of circulatory and respiratory functions of the lung up to 2 to 3 h. However, pharmacological blockade of NOS by L-NNA methyl ester dramatically changed the response to LPS. Administration of LPS arrested all functions of the lung within 6 to 7 mins after its administration. Nonetheless, the most important finding seems to be that after 15 to 25 mins following LPS infusion the lung still remains free of any sign NOS-II mRNA, and it is during that period of time that the early phase of LPS circulatory action occurs and disappears; therefore, any early action of LPS through nitric oxide depends on stimulation of NOS-III because this isoenzyme is present in the lung at that time, contrary to NOS-II. flovent inhaler

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.