EFFECT OF THE INHIBITOR OF NO SYNTHASE, N-G-NITRO-L-ARGININE METHYL-ESTER, ON HISTAMINE-INDUCED BRONCHOSPASM IN THE RABBIT

New Zealand male rabbits were anaesthetized with thiopental, tracheoto mized, curarized by vecuronium bromide and mechanically ventilated. Si x 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 befo re 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 hist amine aerosol, followed by an infusion of L-arginine over a 60-min per iod. Total respiratory resistance (Rrs) and elastance (Ers) were deriv ed by least square analysis of the relationship between tracheal press ure and flow, and computed every minute before and over a l-h period a fter the histamine aerosol. Oxygen free radicals (OFR) were measured w ith a luminometer, in microsomes from lung homogenates at the end of t he experiment. Compared with the histamine response of the control gro up, the Rrs response in the L-NAME 10 group was slightly less, while E rs changes were the same in the two groups. In contrast, L-NAME 15 was responsible for an increased Rrs response, the difference being signi ficant (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 a t 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 predomin antly modulates the response to histamine of the peripheral lung rathe r 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 w as only partially reversed. This suggests that the changes in Ers are partly related to a hardly reversible phenomenon. Possibly, the mechan ical changes are linked with the rise of OFR in the lung parenchyma, w hich were significantly higher in the L-NAME 15 group compared to the control group (P < 0.05).