Capsaicin-induced release of tachykinins: effects of enzyme inhibitors

We studied the effects of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) inhibition on the airway responses and the recovery of endogenously released substance P- and neurokinin A-like immunoreactivities (SP-LI and NKA-LI) after tracheal injection of capsaicin in isolated guinea pig lungs superfused through the trachea. Capsaicin in doses from 10-l ’ to 10m7 mol induced a dose-dependent increase in airway opening pressure and release of SP-LI and NKA-LI. Airway opening pressure changes and the recovery of SP-LI and NKA-LI were significantly greater in lungs superfused with the NEP inhibitor SCH 32615 than in control lungs. ACE inhibition with captopril did not increase the mechanical re-sponse or the recovery of SP-LI compared with lungs not re-ceiving captopril. In lungs from guinea pigs pretreated with high doses of capsaicin 7-10 days before study, a regimen de