Role of nitric oxide synthase types II and III in early protection against endotoxin-induced lung injury (part 2)


In the present study, we report that molecular and immunochemical techniques were unable to detect NOS-II mRNA or NOS-II antigen in the lung up to 25 mins after LPS administration, whereas NOS-III mRNA and NOS-III antigen were invariably detected in the lung of control and LPS-treated rats. Specific mRNA was screened for rat isoforms by reverse transcription polymerase chain reaction (RT-PCR) and confirmed by dot blot and Northern blot analyses. Only 30 mins after starting LPS infusion, NOS-II mRNA and NOS-II antigen appeared simultaneously. NOS-III and NOS-II mRNA were visualized by in situ hybridization technique with nonradioisotope polymerase chain reaction-(PCR) labelled specific cDNA probes, and NOS-III and NOS-II antigens were visualized by histochemical staining with commercial rabbit isoform-specific polyclonal antibodies. buy ortho tri-cyclen
Exogenous nitric oxide donor (S-nitro-N-acetyl-penicyl-lamine [SNAP]) prevented that effect. When a preferential NOS-II inhibitor 1-amino-2-hydroxy-guanidine (AGD) (15mg/kg intravenously) was used instead of L-NNA, there were no pneumotoxic effects of LPS.

We demonstrate that the immediate hypotensive phase of LPS action is associated with activation of NOS-III but not NOS-II in the lung. Moreover, nitric oxide generated in this way does not act as a vasodilator in peripheral circulation but counteracts the injury to pulmonary circulation that is locally inferred by toxic lipids released by LPS in the lung concomitantly.

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.