SENSORY NERVE-MEDIATED AND NEUROPEPTIDE-MEDIATED RELAXATION RESPONSESIN AIRWAYS OF SPRAGUE-DAWLEY RATS

We examined the role of sensory nerves in mediating nonadrenergic inhi bitory responses in airway segments isolated from male Sprague-Dawley rats. In the presence of adrenergic blockade, capsaicin (Cap; 1 mu M) elicited marked relaxation responses in isolated bronchi precontracted with bethanechol (Beth). Cap-induced inhibitory responses were unaffe cted by tetrodotoxin (TTX), were attenuated by incubation of the airwa y with indomethacin (Indo), phosphoramidon, or RP-67580, but were abol ished by previous exposure of the airway to Cap and by denuding the ep ithelium. Substance P (SP; 1 mu M), neurokinins A and B (1 mu M), and calcitonin gene-related peptide (0.1 mu M) relaxed Beth-contracted air way segments to a similar extent. The SP-induced responses were unaffe cted by adrenergic blockade or by pretreatment with either TTX, phosph oramidon, or Cap, but were attenuated by RP-67580 and abolished by Ind o and by denuding the epithelium. In anesthetized mechanically ventila ted rats, Cap (50 and 100 mu g/kg iv) elicited a dose-dependent revers al of the increase in lung resistance induced by an infusion of Beth. The Cap-induced bronchodilation was unaffected by pretreatment with pr opranolol alone or in combination with hexamethonium. SP (44 nmol/kg i v) also evoked bronchodilatory responses in intact animals, which were unaffected by propranolol and hexamethonium but were abolished by tre atment of the animals with Indo. Electrical-field stimulation (EFS) ev oked nonadrenergic noncholinergic relaxation responses in contracted a irway segments. These EFS-induced inhibitory responses were markedly a ttenuated by treatment of the airway segment with TTX, Cap, or RP-6758 0. We conclude that neuropeptides released from Cap-sensitive sensory nerves have potent inhibitory effects in rat airways that are mediated , in part, by activation of neurokonin NK1 receptors on epithelium and subsequent release of an inhibitory prostaglandin(s).