Bradykinin-induced airway microvascular leakage is potentiated by enalaprilat but not by phosphoramidon.
The objective of the study was to determine if bradykinin-induced airway microvascular leakage in rats was altered by pretreatment of animals with enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), or phosphoramidon, an inhibitor of endopeptidase 24.11 (EP 24.11). We found that the intravascular infusion of bradykinin induced microvascular leakage of Evans blue dye in tracheal tissue (0.088 +/- 0.035 micrograms/mg tissue) that was significantly amplified by pretreatment with 3.27 mM enalaprilat (0.458 +/- 0.226 micrograms/mg tissue), but not by pretreatment with 10 mM phosphoramidon (0.082 +/- 0.0453 micrograms/mg tissue). Leakage in carinal tissue was also amplified by pretreatment with 3.27 mM enalaprilat (0.205 +/- 0.050 vs. 0.036 +/- 0.006 micrograms/mg tissue for bradykinin alone), whereas no amplification was observed in parenchymal tissue by pretreatment with either inhibitor. These findings indicate that in the rat, ACE, but not EP 24.11, modulates bradykinin-induced airway microvascular leakage following intravascular infusion of these agents.
Klitzman
D
D
Pulmonary Section, Bronx Veterans Affairs Medical Center, N.Y., N.Y., USA.
Almenoff
P L
PL
Cardozo
C
C
Lesser
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D004357:Drug Synergism; D015773:Enalaprilat / Q000494:pharmacology*; D005070:Evans Blue; D006020:Glycopeptides / Q000494:pharmacology*; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000098:blood supply*
D000806:Angiotensin-Converting Enzyme Inhibitors; D006020:Glycopeptides; D011480:Protease Inhibitors; D005070:Evans Blue; D015260:Neprilysin; D015773:Enalaprilat; D001920:Bradykinin; C008890:phosphoramidon