Effect of vasoactive intestinal peptide on vagally mediated tracheal pouch relaxation

Vasoactive intestinal peptide (VIP) was studied as a possible neurotransmitter of nonadrenergic inhibition in guinea pig tracheas in vivo, by examining the effects of VIP and isoproterenol on pressure changes induced by nerve stimulation in an isolated, fluid filled, tracheal segment (tracheal pouch). VIP though less potent than isoproterenol produced a dose-dependent relaxation of the pouch. Incubation of the histamine-constricted tracheal pouch with isoproterenol resulted in pouch relaxation and a significant (P less than 0.005) loss of pouch responsiveness to sympathetic nerve stimulation, while non-adrenergically mediated pouch relaxation resulting from vagal stimulation in the presence of atropine was inhibited to a much smaller degree. VIP incubation produced relaxation of the histamine-constricted pouch and resulted in a greater loss of responsiveness to vagal than to sympathetic stimulation (P less than 0.02). By demonstrating loss of vagal responsiveness after VIP in guinea pigs, sympathectomized by 6-hydroxydopamine combined with incubation of the pouch with propranolol to eliminate circulating beta adrenergic inhibition, the effects of VIP incubation on vagally induced pouch relaxation were confirmed to be non-adrenergic in nature.