Nitric oxide mediates platelet activating factor-induced microvascular leakage in rat airways.
Platelet activating factor (PAF), a highly potent chemical mediator in inflammation and allergic reactions, induces microvascular leakage in several tissues. In rat airways, PAF-induced microvascular leakage is probably mediated by an endothelial cell receptor in the microvessels. Nitric oxide (NO), first identified as endothelium-derived relaxing factor, has been suggested 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 established. The aim of this study was to investigate the role of NO in PAF-induced microvascular leakage in rat nasal mucosa and trachea. We injected PAF (1 microg/kg) intravenously, and the amount of PAF-induced microvascular leakage was measured with extravasation of Evans blue dye (30 mg/kg, injected intravenously 5 minutes before the injection of PAF) by means of spectrophotometry and fluorescence microscopy. Five Sprague-Dawley rats were pretreated with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, intravenously injected 1 hour before the injection of PAF) to inhibit NO synthase, and control rats (n = 4) were pretreated with normal saline solution. The average amount of extravasated Evans blue dye was significantly lower in the L-NAME-pretreated rats than in the control rats (t-test, p < .01). Tissue sections of the L-NAME-pretreated rats clearly showed a decreased extravasation of Evans blue dye on fluorescence microscopy. In conclusion, pretreatment with L-NAME clearly inhibited PAF-induced microvascular leakage in the nasal mucosa and trachea of rats. This finding implies that PAF may activate the constitutive endothelial NO synthase in the microvessels, and that activated endogenous NO may mediate PAF-induced microvascular leakage in rat airways.
Jeon
S Y
SY
Department of Otolaryngology, GyeongSang National University Hospital, Chinju, Korea.
Kim
E A
EA
Ma
Y W
YW
Kim
J P
JP
Jung
T G
TG
Hwang
E G
EG
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D004396:Coloring Agents; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005070:Evans Blue; D005260:Female; D008856:Microscopy, Fluorescence; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009297:Nasal Mucosa / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000098:blood supply*
D004396:Coloring Agents; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D009569:Nitric Oxide; D005070:Evans Blue; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester