Effect of the inhibitor of NO synthase, NG-nitro-L-arginine methyl ester, on histamine-induced bronchospasm in the rabbit.
New Zealand male rabbits were anaesthetized with thiopental, tracheotomized, curarized by vecuronium bromide and mechanically ventilated. Six rabbits received L-NAME 10 mg kg-1 i.v., six rabbits L-NAME 15 mg kg-1 iv, and six rabbits received saline i.v. (controls), 5 min before a histamine aerosol (2% solution during 5 min). Six others rabbits received an injection of L-NAME 15 mg kg-1 iv, 5 min before the histamine aerosol, followed by an infusion of L-arginine over a 60- min period. Total respiratory resistance (Rrs) and elastance (Ers) were derived by least square analysis of the relationship between tracheal pressure and flow, and computed every minute before and over a 1-h period after the histamine aerosol. Oxygen free radicals (OFR) were measured with a luminometer, in microsomes from lung homogenates at the end of the experiment. Compared with the histamine response of the control group, the Rrs response in the L-NAME 10 group was slightly less, while Ers changes were the same in the two groups. In contrast, L-NAME 15 was responsible for an increased Rrs response, the difference being significant (P < 0.05) only between 15 and 40 min after the aerosol (+114% vs. +85% in controls at the 20th min). The increase in Ers with L-NAME 15 was stronger and significantly larger (+71% vs. +42% in controls at the 20th min after the histamine aerosol, P < 0.001). The relatively greater effect of L-NAME on Ers than on Rrs suggests that NO predominantly modulates the response to histamine of the peripheral lung rather than that of the large airways. Furthermore, the effect of L-NAME on Rrs was completely abolished by L-arginine, while its effect on Ers was only partially reversed. This suggests that the changes in Ers are partly related to a hardly reversible phenomenon. Possibly, the mechanical changes are linked with the rise of OFR in the lung parenchyma, which were significantly higher in the L-NAME 15 group compared to the control group (P < 0.05).
Dewachter
P
P
Department d'Anesthésiologie, Hôpital central, Nancy, France.
Vassiliou
M
M
Saunier
C G
CG
Hartemann
D
D
Peslin
R
R
Laxenaire
M C
MC
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001986:Bronchial Spasm / Q000139:chemically induced / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005609:Free Radicals; D006632:Histamine; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010100:Oxygen / Q000097:blood; D011817:Rabbits; D017382:Reactive Oxygen Species; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D005609:Free Radicals; D017382:Reactive Oxygen Species; D006632:Histamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester