The effect of a nitric oxide synthase inhibitor on the modulation of airway responsiveness in rats.
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.
Kips
J C
JC
Department of Respiratory Diseases, University Hospital Ghent, Belgium.
Lefebvre
R A
RA
Peleman
R A
RA
Joos
G F
GF
Pauwels
R A
RA
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D007958:Leukocyte Count; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D009569:Nitric Oxide; D002217:Carbachol; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester