Endogenous nitric oxide contributes to strain-related differences
in airway responsiveness in rats.
Jia, Yanlin, Lijing Xu, Debra J. Turner, and James G. Martin.
Montreal Chest Institute Research Centre and Meakins-Christie
Laboratories, McGill University, Montreal, Quebec, Canada, H2X
2P2
APStracts 2:0422A, 1995.
The effects of N_-nitro-L-arginine (L-NNA), a nitric oxide synthase
(NOS) inhibitor, on airway responsiveness were studied in the
spontaneously hyperresponsive Fisher 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 (MCh) was
significantly increased in L-NNA-treated Lewis rats but not in Fisher
rats. L-NNA increased carbachol-induced tracheal contractions in
vitro to a larger extent in Lewis rats compared with Fisher rats. The
effect of L-NNA was abolished by removal of the epithelium. Carbachol
induced a NO-dependent increase in cyclic GMP levels in tracheal
tissues, but to a lesser extent in Fisher (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-cyclic GMP regulatory
mechanism in Fisher rats contributes, in part, to strain related
differences in airway responsiveness between Fisher and Lewis rats.
Received 17 February 1995; accepted in final form 11 September
1995.
APS Manuscript Number A191-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95