Increased airway osmolarity inhibits the action of nitric oxide in the rabbit

Inhalation of nitric oxide (NO) is known to dilate preconstricted airways,I n asthmatics, there are large variations in the effect of NO on airway tone . One explanation of these variations may be different degrees of airway wa ll oedema, The effect of NO inhalation on methacholine (meth)-induced airway constrict ion was investigated in a rabbit model. Oedema and a change in osmolarity o f the airways was achieved by hypertonic saline nebulization and hyperventi lation with dry gas. There was an increase in resistance to meth at a concentration of 3 mg.mL(- 1) of 86+/-14 cmH(2)O.L-1.s (mean+/-SEM) after oedema formation, compared w ith 46+/-16 cmH(2)O.L-l.s without oedema, Inhalation of 80 parts per millio n (ppm) NO failed to counter the increase in resistance due to meth, 92+/-1 4 cmH(2)O.L-1.s after hypertonic saline nebulization, After hyperventilatio n of dry gas, the increase in resistance due to meth at 1 mg.mL(-1) was 27/-11 cmH(2)O.L-1.s with 80 ppm NO and 28+/-5 cmH(2)O.L-1.s without NO. In conclusion, the relaxant effect of nitric oxide-inhalation on the airway smooth muscle can be blocked by an increase in the osmolarity of the airwa y surface liquid. The mechanism of this inhibition of nitric oxide remains to be established.