Comparison of vasoactive intestinal peptide and isoproterenol relaxant effects in isolated cat airways

Vasoactive intestinal peptide (VIP), an endogenous peptide found in mammalian tissues including the lung, is a potent relaxant of smooth muscle. In precontracted segments of cat trachea, hilar bronchus, and intrapulmonary bronchus, concentration-relaxation curves to VIP were compared with those produced by isoproterenol. VIP and isoproterenol were nearly equipotent in causing relaxation of extrapulmonary airways. A decreasing sensitivity to VIP was observed in progressively smaller airways, suggesting regional variation in VIP-induced responses. In contrast, tissues showed no regional differences in response to isoproterenol. Propranolol (10(-6) M), which antagonized relaxation responses to isoproterenol, had no effect on VIP concentration-response curves. Indomethacin (10(-5) M) completely prevented responses to exogenous arachidonic acid but did not inhibit VIP-induced relaxation. Avian pancreatic polypeptide, which has been reported to inhibit vasodilator responses to VIP in the cat, was unable to antagonize airway smooth muscle relaxation induced by VIP. These results demonstrate that VIP is a potent relaxant of cat tracheobronchial smooth muscle in vitro and that the relaxant effects of this peptide are not mediated through beta-adrenergic receptors or by prostaglandins. In view of previous reports on the localization of VIP immunoreactivity in nerves around airways in cat lung, results of the present study suggest that VIP may participate in the regulation of airway tone in this species.