Role of nitric oxide in allergic inflammation and bronchial hyperresponsiveness.
The role of nitric oxide (NO) in allergic inflammation and bronchial hyperresponsiveness is unclear. We studied a selective prodrug nitric oxide synthase (NOS)-2 inhibitor, L-N(6)-(1-iminoethyl)lysine 5-tetrazole amide (SC-51). In ovalbumin-sensitized and challenged rats, exhaled NO levels increased by 3 h following challenge (3.73 +/- 0.74 ppb; P < 0.05), peaking at 9 h (11.0 +/- 2.75; P < 0.01) compared to saline controls (1.87 +/- 0.26; P < 0.05 and 2.81 +/- 0.18; P < 0.01). Immunoreactive lung NOS2 expression was increased in ovalbumin-challenged rats compared with ovalbumin-sensitized, saline-challenged rats at 8 h post-challenge. SC-51 (10 mg/kg; p.o.) inhibited allergen-induced increase in exhaled NO levels to 1.3 +/- 0.17 ppb. SC-51 inhibited bronchial hyperresponsiveness in ovalbumin-sensitized and challenged rats (P < 0.05). In sensitized non-exposed rats, SC-51 increased bronchial responsiveness (P < 0.05). SC-51 reduced the allergen-induced increase in bronchoalveolar lavage neutrophils, but caused a nonsignificant reduction in bronchial mucosal eosinophil numbers. NO generated through NOS2 contributes to allergen-induced bronchial hyperresponsiveness but not to bronchial eosinophilia, indicating that these are independently expressed.
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism; D006709:Homoarginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006967:Hypersensitivity / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008168:Lung / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN
D004791:Enzyme Inhibitors; D007527:Isoenzymes; C446200:L-N(6)-(1-iminoethyl)lysine tetrazole-amide; D006709:Homoarginine; D009569:Nitric Oxide; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D000109:Acetylcholine