This study examines the role of endogenous nitric oxide (NO) in airway microvascular leakage induced by inflammatory mediators, which play an important role in asthmatic airways. Guinea-pigs were anaesthetized and mechanically-ventilated with monitoring of arterial blood pressure, and airway microvascular leakage induced by intravenous injection of substance P (SP), leukotriene D4 (LTD4) and histamine was evaluated using Evans blue dye and Monastral blue dye in the presence and absence of the NO synthase inhibitors, L-N(G)-nitroarginine methyl ester (L-NAME) and L-N(G)-monomethyl arginine (L-NMMA). The effect of a soluble guanylate cyclase inhibitor, LY83583, on SP-induced dye leakage was also examined. Intravenous injection of SP (1 μg · kg-1), LTD4 (1 μg · kg-1) and histamine (100 μg · kg-1) significantly increased dye extravasation at all airway levels. Pretreatment with L-NAME (10 mg · kg-1 i.v.) and L-NMMA (100 mg · kg-1 i.v.) significantly inhibited SP-induced extravasation, and L-arginine (100 mg · kg-1 i.v.) reversed L-NAME-induced inhibition. L-NAME (10 mg · kg-1 i.v.) also significantly inhibited LTD4-induced dye extravasation only in central airways, and this inhibitory effect was abolished by a neurokinin-1 (NK1) antagonist, FK888 (10 mg · kg-1 i.v.) pretreatment. Histamine-induced dye extravasation was not affected by L-NAME. LY83583 (2.5 and 7.5 mg · kg-1 i.v.) partially but significantly reduced SP-induced dye leakage. These results suggest that endogenous nitric oxide plays a role in neurokinin-1 receptor-mediated airway microvascular leakage, and presumably involves the guanylate cyclase pathway.
- airway plasma leakage
- leukotriene D
- neurokinin-1 receptor
- nitric oxide synthase inhibitor
- substance P
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine