Endogenous nitric oxide contributes to strain-related differences in airway responsiveness in rats.
The effects of N(omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, on airway responsiveness were studied in the spontaneously hyperresponsive Fischer and the control normoresponsive Lewis rat strains to investigate the role of the endogenous nitric oxide (NO) pathway in strain-related differences in airway responsiveness. Responsiveness to inhaled methacholine was significantly increased in L-NNA-treated Lewis rats but not in Fischer rats. L-NNA increased carbachol-induced tracheal contractions in vitro to a larger extent in Lewis rats compared with Fischer rats. The effect of L-NNA was abolished by removal of the epithelium. Carbachol induced a NO-dependent increase in guanosine 3',5'-cyclic monophosphate levels in tracheal tissues but to a lesser extent in Fischer (2.1-fold increase) than in Lewis (3.7-fold increase) rats. In conclusion, endogenous NO is involved in the regulation of airway responsiveness to cholinergic agonists in rats. A relatively ineffective NO-guanosine 3',5'-cyclic monophosphate regulatory mechanism in Fischer rats contributes, in part, to strain-related differences in airway responsiveness between Fischer and Lewis rats.
Jia
Y
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Montreal Chest Institute Research Centre and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Xu
L
L
Turner
D J
DJ
Martin
J G
JG
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015656:Respiratory Mechanics / Q000502:physiology*; D013045:Species Specificity; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D016210:Methacholine Chloride; D019335:Nitroarginine; D009569:Nitric Oxide; D002217:Carbachol; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP