Cyclic nucleotide metabolism in experimental bronchial constriction in rabbits

In anesthetized, spontaneously breathing rabbits, intratracheally administered isotonic saline, acetylcholine (Ach) and histamine (His) induced an increase of airway resistance up to 183, 571, and 312%, respectively, compared with untreated controls. This was accompanied by a decrease of the arterial pO2. Bilateral cervical vagotomy led to nearly complete inhibition of the saline- and Ach-induced bronchoconstriction, whereas the His effect was only reduced to 202%. Vagotomy did not improve the arterial pO2. While the bronchoconstrictive effects of isotonic saline and Ach revealed a significant linear correlation with the increased cGMP/cAMP ratio, His did not cause an alteration of the cGMP/cAMP ratio to a degree that corresponds to its bronchoconstrictive activity. These data indicate that (1) bronchoconstriction-inducing agents may act (a) by stimulation of the parasympathetic nerve or (b) by contracting smooth muscles directly; (2) alveolar ventilation is not regulated by the parasympathetic nerve, and (3) bronchoconstriction induced by parasympathetic stimulation is associated with or mediated by an increase of the cGMP/cAMP ratio.