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The effect of peptidase inhibitors on bradykinin‐induced bronchoconstriction in guinea‐pigs in vivo
Author(s) -
Ichinose Masakazu,
Barnes Peter J.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12092.x
Subject(s) - phosphoramidon , bradykinin , thiorphan , bronchoconstriction , captopril , neprilysin , propranolol , chemistry , endocrinology , enzyme inhibitor , medicine , enalaprilat , pharmacology , angiotensin converting enzyme , ace inhibitor , enzyme , blood pressure , biochemistry , receptor , asthma
1 Bradykinin (BK) instilled directly into the airway lumen caused bronchoconstriction in anaesthetized, mechanically ventilated guinea‐pigs in the presence of propranolol (1 mg kg −1 i.v.) The geometric mean dose of BK required to produce 100% increase in airway opening pressure (PD 100 ) was 22.9 nmol (95% c.i. 11.7–44.6 nmol). 2 The dose‐response curve for the effect of instilled BK was significantly shifted to the left by the angiotensin converting enzyme (ACE) inhibitor, captopril (5 and 50 nmol instillation, PD 100 = 3.0, 95% c.i. 0.98–8.9, and 2.0 nmol, 95% c.i. 0.65–6.2 nmol, respectively). 3 The neutral endopeptidase (NEP) inhibitor, phosphoramidon (5 and 50 nmol instillation) also shifted the dose‐response curve for the effect of instilled BK; the PD 100 values = 2.2 (95% c.i. 0.40–11.7) and 1.8 nmol (95% c.i. 0.87–3.5 nmol), respectively. 4 After pretreatment with captopril (50 nmol) and phosphoramidon (50 nmol) in combination, the dose‐response curve for the effect of instilled BK (PD 100 =1.1 nmol, 95% c.i. 0.37–3.2 nmol) was similar to that obtained in the presence of each inhibitor used alone. 5 The kininase I inhibitor, dl ‐2‐mercaptomethyl‐3‐guanidinoethylthiopropionic acid (50 nmol instillation) failed to alter the dose‐response curve to instilled BK (PD 100 = 14.6 nmol, 95% c.i. 6.7–32.0 nmol). 6 These data suggest that both ACE and NEP degrade BK in the airway lumen, but that kininase I is not involved.