Sensory nerve- and neuropeptide-mediated relaxation responses in airways of Sprague-Dawley rats

Abstract

We examined the role of sensory nerves in mediating nonadrenergic inhibitory responses in airway segments isolated from male Sprague-Dawley rats. In the presence of adrenergic blockade, capsaicin (Cap; 1 microM) elicited marked relaxation responses in isolated bronchi precontracted with bethanechol (Beth). Cap-induced inhibitory responses were unaffected by tetrodotoxin (TTX), were attenuated by incubation of the airway with indomethacin (Indo), phosphoramidon, or RP-67580, but were abolished by previous exposure of the airway to Cap and by denuding the epithelium. Substance P (SP; 1 microM), neurokinins A and B (1 microM), and calcitonin gene-related peptide (0.1 microM) relaxed Beth-contracted airway segments to a similar extent. The SP-induced responses were unaffected by adrenergic blockade or by pretreatment with either TTX, phosphoramidon, or Cap, but were attenuated by RP-67580 and abolished by Indo and by denuding the epithelium. In anesthetized mechanically ventilated rats, Cap (50 and 100 micrograms/kg i.v.) elicited a dose-dependent reversal of the increase in lung resistance induced by an infusion of Beth. The Cap-induced bronchodilation was unaffected by pretreatment with propranolol alone or in combination with hexamethonium. SP (44 nmol/kg iv) also evoked bronchodilatory responses in intact animals, which were unaffected by propranolol and hexamethonium but were abolished by treatment of the animals with Indo. Electrical-field stimulation (EFS) evoked nonadrenergic noncholinergic relaxation responses in contracted airway segments. These EFS-induced inhibitory responses were markedly attenuated by treatment of the airway segment with TTX, Cap, or RP-67580. 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).