Pulmonary C-fiber activation before and after peptidase inhibition in rats.
Inhibition of peptidases within the lungs not only potentiates the effects of neuropeptides released from C-fibers but also the effects of bradykinin and capsaicin both of which stimulate C-fibers. To determine if peptidase inhibition potentiates C-fiber activation, we challenged pulmonary C-fibers in rats with capsaicin or bradykinin before and after inhibition of neutral endopeptidase (NEP) or angiotensin converting enzyme (ACE). Inhibition of NEP by phosphoramidon (10 mg/kg, i.v.) potentiated the effect of capsaicin (0.5-1 micrograms, i.v.) on C-fiber activity but did not change the response to bradykinin (1-2 micrograms, i.v.). Inhibition of ACE by captopril (5 mg/kg, i.v.) potentiated C-fiber activation by either bradykinin or capsaicin. Aerosol administration of either phosphoramidon (1 x 10(-5) M, 2 min) or captopril (4.6 x 10(-3) M, 2 min) potentiated C-fiber activation by capsaicin aerosol (1.6 x 10(-4) M, 1 min) but not by bradykinin aerosol (9.4 x 10(-5) M, 1 min). Therefore, inhibition of NEP or ACE may potentiate airway obstructive mechanisms initiated by C-fiber stimulation.
Bergren
D R
DR
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha NE 68178, USA.
Ustinova
E E
EE
Schultz
H D
HD
D000280:Administration, Inhalation; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D006020:Glycopeptides / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000294:innervation*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D006020:Glycopeptides; D011480:Protease Inhibitors; D002268:Carboxypeptidases; D015260:Neprilysin; D002211:Capsaicin; D001920:Bradykinin; C008890:phosphoramidon