Inhibition of guanylyl cyclase in the airways hyperreactivity

Abstract

Background: The majority of nitric oxide (NO) effects in the respiratory system are mediated via the stimulation of soluble guanylyl cyclase with subsequent generation of the second messenger--cyclic guanosine monophosphate (cGMP).

Objectives: We were interested in the effect of non-selective soluble guanylyl cyclase inhibitor--methylene blue on the exogenous irritant-induced bronchial hyperreactivity.

Methods: Male guinea pigs were used in the experiment. The animals received non-selective soluble guanylyl cyclase inhibitor--methylene blue in a dose of 50 or 100 mg/kg b.w. 30 minutes before inhalation of the exogenous irritant--toluene vapours. The toluene exposition lasted three consecutive days during two hours in in vivo conditions. The monitoring of tracheal and lung tissue strips reactivity changes was carried out in in vitro conditions. The brochoconstrictor mediators histamine and acetylcholine in the cumulative doses (10(-8)-10(-3) mol/l) were used in the experiment.

Results: The methylene blue pretreatment induced the decrease of tracheal and lung tissue smooth muscle contraction amplitude increased by exogenous irritant--toluene. We recorded different smooth muscle response depending on the doses of inhibitor. Methylene blue in a dose of 50 mg/kg b.w. affected mainly tracheal smooth muscle, in a dose of 100 mg/kg b.w. mainly the lung tissue.

Conclusion: The interaction between nitric oxide and soluble guanylyl cyclase can be important for bronchial reactivity changes. The changes depended on the dose of inhibitor and on the type of respiratory system tissue (trachea, lung). We can summarise that changes of the airways reactivity are not only evoked by NO/cGMP pathway but probably by any other mechanisms (Fig. 5, Ref. 26).