EFFECTS OF CHRONIC AIRWAY INFLAMMATION ON THE ACTIVITY AND ENZYMATIC INACTIVATION OF NEUROPEPTIDES IN GUINEA-PIG LUNGS

The effects of airway inflammation induced by chronic antigen exposure on substance P (SP)-induced increases and vasoactive intestinal pepti de(VIP) -induced decreases in airway opening pressure (Pao), and the r ecovery of intact and hydrolyzed radiopeptide were studied in tracheal ly perfused guinea pig lungs. SP (10(-6) mol/kg) induced a significant ly greater increase in Pao in lungs from antigen-exposed (30 +/- 5 cm H2O) than saline-exposed animals(15 +/- 1 cm H2O, P < 0.05). Significa ntly more intact H-3-SP and significantly less H-3-SP 1-7, a neutral e ndopeptidase(NEP) hydrolysis product, were recovered from the lung eff luent of antigen-exposed than saline-exposed animals (P < 0.05). Injec tion of VIP (10(-9) mol/kg) induced significantly more pulmonary relax ation in saline-exposed compared with antigen-exposed lungs (62 +/- 4% , P < 0.001). In contrast to effluent from saline-exposed animals, lun g effluent from antigen-exposed lungs contained less intact VIP, incre ased amounts of a tryptic hydrolysis product, and no products consiste nt with the degradation of VIP by NEP. These data indicate that inflam ed lungs are more sensitive to the contractile effects of SP because i t is less efficiently degraded by NEP and are less sensitive to the re laxant effects of VIP because it is more efficiently degraded by a try ptic enzyme. Changes in airway protease activity occur with allergic i nflammation and may contribute to airway hyperresponsiveness.