Endogenous nitric oxide modifies antigen-induced microvascular leakage in sensitized guinea pig airways.
To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (l-NAME), on antigen-induced airway microvascular leakage in actively sensitized guinea pigs by using Evans blue dye. Three weeks after sensitization with ovalbumin (10 micrograms), the tracheas were cannulated, and lungs were artificially ventilated. Animals were pretreated with atropine and propranolol (both 1 mg/kg, intravenously) to avoid neural modification. Ovalbumin inhalation (3 mg/ml, 1 minute) challenge caused significant microvascular leakage in all airways portions, which was significantly suppressed in a dose-dependent manner by pretreatment with intravenous injection of L-NAME (1 and 10 mg/kg) but not with the inactive enantiomer D-NAME (10 mg/kg). This inhibition by L-NAME was significantly reversed by co-administration of L-arginine (100 mg/kg, intravenously). Pretreatment with a vasoconstrictor, phenylephrine (20 micrograms/kg, intravenously), had no inhibitory effects on antigen-induced airway microvascular leakage despite increasing systemic blood pressure. Inhalation of representative mast cell-derived mediators, histamine (2 mg/ml, 1 minute) or leukotriene D4 (5 micrograms/ml, 1 minute), produced significant microvascular leakage in all airways. L-NAME (10 mg/kg, intravenously) partially but significantly inhibited leukotriene D4-induced leakage, whereas histamine-induced leakage was not affected. These results suggest that endogenous nitric oxide acts to increase airway microvascular leakage after airway allergic reaction.
Miura
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ichinose
M
M
Kageyama
N
N
Tomaki
M
M
Takahashi
T
T
Ishikawa
J
J
Ohuchi
Y
Y
Oyake
T
T
Endoh
N
N
Shirato
K
K
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology*; D006168:Guinea Pigs; D018836:Inflammation Mediators / Q000494:pharmacology; D007442:Intubation, Intratracheal; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000276:immunology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000941:Antigens; D018836:Inflammation Mediators; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester