TY - JOUR
T1 - Endogenous nitric oxide modifies antigen-induced microvascular leakage in sensitized guinea pig airways
AU - Miura, Motohiko
AU - Ichinose, Masakazu
AU - Kageyama, Natsuko
AU - Tomaki, Masafumi
AU - Takahashi, Tsuneyuki
AU - Ishikawa, Jun
AU - Ohuchi, Yuzuru
AU - Oyake, Tatsuya
AU - Endoh, Naomi
AU - Shirato, Kunio
PY - 1996
Y1 - 1996
N2 - To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, Nω-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 μg), 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 airway 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 μg/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 μg/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.
AB - To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, Nω-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 μg), 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 airway 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 μg/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 μg/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.
KW - L-NAME
KW - L-arginine
KW - histamine
KW - leukotriene D
KW - mast cell degranulation
KW - ovalbumin
UR - http://www.scopus.com/inward/record.url?scp=0029782023&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029782023&partnerID=8YFLogxK
U2 - 10.1016/S0091-6749(96)70236-1
DO - 10.1016/S0091-6749(96)70236-1
M3 - Article
C2 - 8765828
AN - SCOPUS:0029782023
VL - 98
SP - 144
EP - 151
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 1
ER -