ADRENERGIC AND CHOLINERGIC INTERACTION IN CENTRAL VENTILATORY CONTROL

The ventrolateral medulla, which functions as integrator of cardiorespiratory control, contains cholinergic and adrenergic neurons. Exogenously administered cholinergic and adrenergic agents affect both ventilation and circulation. It is not clear whether these agents act in an independent or coordinate manner. β-Adrenergic and α2-adrenergic agents stimulate and depress the cardiorespiratory system, respectively. β-Adrenergic and α2-adrenergic agents stimulate and depress the production of adenosine 3',5'-cyclic monophosphate (cAMP), respectively. Increased intracellular cAMP may facilitate the release of acetylcholine (ACh). This work seeks to answer the following questions: 1) Are the cardiorespiratory effects of adrenergic agents secondary to possible changes in ACh release? 2) Does cAMP production have an intermediate role? By means of ventriculocisternal perfusion in anesthetized (pentobarbital sodium, 30 mg/kg) spontaneously breathing dogs, isoproterenol (ISO) increased ventilation (V̇E) 75% (P < 0.05); heart rate and cardiac output were also increased (P < 0.05). Esmolol (a β-antagonist) blocked both the cardiovascular and ventilatory effects of ISO. Atropine (a cholinergic antagonist) blocked the ventilatory effects of ISO, but the circulatory changes persisted. Forskolin (a direct activator of adenylate cyclase) increased V̇E 51% (P < 0.05), and its effect was also blocked by atropine. Clonidine decreased V̇E 42% (P < 0.05); heart rate and cardiac output were also decreased. The ventilatory depressant effects of clonidine were offset by the coadministration of ACh. The data suggest that only the ventilatory effects of adrenergic agents may involve changes in ACh release. The generation of cAMP may be an important intermediate step in this process, because forskolin mimics the effects of ISO on ventilation.