Effects of peptidase inhibitors on bradykinin-induced bronchoconstriction in the rat.
Objectives of this study were to determine if aerosolized bradykinin causes bronchoconstriction in anesthetized, mechanically ventilated rats, and if pretreatment with enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), or phosphoramidon, an inhibitor of endopeptidase 24.11 (EP 24.11), alters the response. We found that aerosolized bradykinin elicited a reproducible bronchoconstrictor response that was significantly amplified by pretreatment with aerosolized enalaprilat or phosphoramidon. Neither inhibitor alone affected airway tone or caused nonspecific airway hyperreactivity. These findings indicate that both ACE and EP 24.11 contribute to bradykinin degradation in rat airways.
Schilero
G J
GJ
Department of Medicine, Mount Sinai School of Medicine, New York, NY.
Almenoff
P
P
Cardozo
C
C
Lesser
M
M
D000336:Aerosols; D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology*; D006020:Glycopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008448:Maximal Expiratory Flow Rate / Q000187:drug effects; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors
D000336:Aerosols; D006020:Glycopeptides; D011480:Protease Inhibitors; D015260:Neprilysin; D015773:Enalaprilat; D001920:Bradykinin; C008890:phosphoramidon