Nitric oxide mediates platelet activating factor-induced microvascular leakage in rat airways

Platelet activating factor (PAF), a highly potent chemical mediator in infl ammation and allergic reactions, induces microvascular leakage in several t issues. In rat airways. PAF-induced microvascular leakage is probably media ted by an endothelial cell receptor in the microvessels. Nitric oxide (NO), first identified as endothelium-derived relaxing factor, has been suggeste d to be a mediator of airway microvascular leakage. However, the role of NO in PAF-induced microvascular leakage in the airways has not yet been estab lished. The aim of this study was to investigate the role of NO in PAF-indu ced microvascular leakage in rat nasal mucosa and trachea. We injected PAF (1 mug/kg) intravenously, and the amount of PAF induced microvascular leaka ge was measured with extravasation of Evens blue dye (30 mg/kg, injected in travenously 5 minutes before the injection of PAF) by means of spectrophoto metry and fluorescence microscopy. Five Sprague Dawley rats were pretreated with NG-nitro-L-arginine methylester(L-NAME; 10 mg/kg, intravenously injec ted 1 hour before the injection of PAF) to inhibit NO synthase, and control rats (n = 4) were pretreated with normal saline solution. The average amou nt of extravasated Evans blue dye was significantly lower in the L-NAME-pre treated rats than in the control rats (t-test, p <.01). Tissue sections of the L-NAME-pretreated rats clearly showed a decreased extravasation of Evan s blue dye on fluorescence microscopy. In conclusion, pretreatment with L-N AME clearly inhibited PAF-induced microvascular leakage in the nasal mucosa and trachea of rats. This finding implies that PAF may activate the consti tutive endothelial NO synthase in the microvessels, and that activated endo genous NO may mediate PAF-induced microvascular leakage in rat airways.