Am. J. Respir. Crit. Care Med., Vol 151, No. 4, 04 1995, 1165-1169.
The effect of a nitric oxide synthase inhibitor on the modulation of airway responsiveness in rats
JC Kips, RA Lefebvre, RA Peleman, GF Joos and RA Pauwels
Department of Respiratory Diseases, University Hospital Ghent, Belgium.
The possible role of nitric oxide (NO) in the regulation of airway tone
remains to be fully explored. In the present study we examined the effect
of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase,
on airway responsiveness in rats. The effect of L-NAME on endotoxin
(lipopolysaccharide; LPS)-induced changes in airway responsiveness was also
evaluated. L-NAME (1 mg/kg given intravenously) caused a 33.3 +/- 6.9%
increase in blood pressure, but did not influence baseline airway tone or
the provocative dose of carbachol causing a 50% increase in pulmonary
resistance (RL)(PD50RL). Exposure of F344 rats to LPS induced a transient
increase in airway responsiveness at 90 min after exposure, followed by a
significant hyporesponsiveness between 9 and 12 h after exposure. L-NAME (1
mg/kg intravenously) did not influence the increase in responsiveness but
inhibited the LPS-induced hyporesponsiveness; in LPS-exposed, L-NAME-
treated animals, the PD50RL for carbachol was 3.0 +/- 0.1, versus 4.8 +/-
0.3 micrograms/kg in the LPS-exposed, placebo-pretreated group (p <
0.05). The effect of L-NAME was abolished by pretreatment with L- arginine
but not with D-arginine. L-NAME did not influence the LPS- induced increase
of neutrophils in bronchoalveolar lavage fluid (BALF). These results
suggest that in rats, consitutive NO synthesis does not contribute either
to basal airway tone or to the basal degree of airway responsiveness, but
that inducible NO synthesis mediates endotoxin- induced hyporesponsiveness.
