When the preferential NOS-II inhibitor AGD (15 mg/kg intravenously) (Figure 2) was given instead of L-NNA before LPS infusion, survival time was lengthened compared with that of LPS-treated rats. These data suggest that the release of nitric oxide in the early phase of endotoxemia may prevent acute pneumotoxicity of LPS caused by platelet-activating factor, thromboxane A2 or sulphidopeptide leukotrienes . On the other hand, the significant elongation of survival time by changing L-NNA to AGD in the basal model of endotoxemia supported the view that during the chronic late phase of LPS action, most of the nitric oxide is generated by NOS-II.On the basis of these results, we postulate that nitric oxide, depending on whether it originates from NOS-III or from NOS-II, plays two different roles in endotoxemia. NOS-III-derived nitric oxide protects the lung against early endotoxe-mic lipid-mediated injury, whereas NOS-II-derived nitric oxide, which appears during the late phase of endotoxemia, is a toxic agent of essential influence on lethal hypotension and vasoplegia. buy levaquin online
By using RT-PCR, in situ hybridization and immunochemical techniques, only NOS-III mRNA and NOS-III antigen were detected in the lung 15 mins and 25 mins (data not shown) after LPS infusion (Figure 3). No traces of NOS-II mRNA (Figure 5) or NOS-II antigen (data not shown) were detected.