In Vivo Demonstration of Nonadrenergic Inhibitory Innervation of the Guinea Pig Trachea

Abstract

To determine if electrical stimulation of autonomic nerves could excite nonadrenergic inhibitory motor pathways in the guinea pig respiratory system in vivo, we studied the effects of electrical stimulation of the cervical vagi and sympathetic nerve trunks on pressure changes (P_p) within an isolated, fluid-filled cervical tracheal segment which reflected changes in trachealis muscle tone. We preserved the innervation and circulation of the segment as evidenced by a rise in P_p with vagus nerve stimulation and a fall in P_p with intravenous isoproterenol. In five atropine-treated animals, stimulation of the cut vagi or sympathetic nerve trunks resulted in a mean fall in P_p of 7.9 and 8.2 cm H₂O, respectively. Treatment with propranolol attenuated the response to sympathetic stimulation but not vagal stimulation. To determine if these relaxation responses were mediated by an adrenergic or nonadrenergic mechanism, we studied an additional five animals that had been treated with 6-hydroxydopamine to destroy adrenergic nerve endings. In 6-hydroxydopamine, atropine, and propranolol-treated animals, sympathetic nerve stimulation decreased P_p only 0.65 cm H₂O, confirming the elimination of adrenergic nerve influences, whereas vagus nerve stimulation decreased P_p 17.7 cm H₂O. After sectioning the recurrent laryngeal nerves, the mean decrease in P_p during vagus nerve stimulation was only 3.2 cm H₂O. These findings demonstrate the presence of nonadrenergic inhibitory nerves in the guinea pig trachea in vivo. They further show that nonadrenergic inhibitory nerve effects are elicited during electrical stimulation of the vagus nerves and that interruption of the recurrent laryngeal nerves diminishes the magnitude of these effects.