Protection from experimental asthma by an endogenous bronchodilator.
Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, wild-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma.
Que
Loretta G
LG
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Liu
Limin
L
Yan
Yun
Y
Whitehead
Gregory S
GS
Gavett
Stephen H
SH
Schwartz
David A
DA
Stamler
Jonathan S
JS
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000426:Alcohol Dehydrogenase; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001980:Bronchi; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D001993:Bronchodilator Agents; D005260:Female; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D007097:Imines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin; D026422:S-Nitrosoglutathione / Q000378:metabolism* / Q000494:pharmacology; D026403:S-Nitrosothiols / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D000485:Allergens; D001993:Bronchodilator Agents; D007097:Imines; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D026403:S-Nitrosothiols; D016210:Methacholine Chloride; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D010047:Ovalbumin; C483598:Adh5 protein, mouse; D000426:Alcohol Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005980:Glutathione Reductase; D007545:Isoproterenol