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SYNERGISTIC POTENTIATION BY CAPTOPRIL AND PROPRANOLOL OF BRADYKININ‐INDUCED BRONCHOCONSTRICTION IN THE GUINEA‐PIG
Author(s) -
Lau W. A. K.,
Rechtman M. P.,
Boura A. L. A.,
King R. G.
Publication year - 1989
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1989.tb01524.x
Subject(s) - bronchoconstriction , bradykinin , captopril , histamine , chemistry , medicine , propranolol , endocrinology , thromboxane , thromboxane a2 , pharmacology , receptor , asthma , platelet , blood pressure
SUMMARY 1. Captopril (30 or 100 μg/kg intravenous (i.v.)) in anaesthetized artificially ventilated guinea‐pigs potentiated bronchoconstrictor responses to bradykinin, but not those to histamine or the thromboxane A 2 ‐mimetic U46619. 2. Propranolol (5 mg/kg, i.v.) potentiated bradykinin‐induced bronchoconstriction. The potentiated responses were further augmented by captopril. 3. The captopril‐potentiated responses to bradykinin were inhibited during cyclo‐oxygenase inhibition with indomethacin. Bronchoconstrictor responses to bradykinin, but not those to histamine or U46619, were reduced after thromboxane synthase inhibition with dazoxiben. The thromboxane A 2 antagonist AH23848 inhibited bronchoconstrictor responses to bradykinin, arachidonic acid or U46619 whereas it did not affect those to histamine. 4. A kininase I inhibitor dl ‐2‐mercaptomethyl‐3‐guanidinoethyl thiopropanoic acid caused no change in bronchoconstriction caused by bradykinin and did not alter the potentiated responses occurring after captopril. 5. Thus, confirmation has been obtained that bradykinin causes bronchoconstriction in the guinea‐pig indirectly, by release of eicosanoids. Thromboxane A 2 is likely to be the major eicosanoid released, since the bronchoconstrictor effect of bradykinin was blocked by indomethacin, dazoxiben and AH23848. The intensity of the bronchoconstriction appears dependent on sympathetic influences mediated by β‐adrenoceptors. Kininase I, in contrast to kininase II apparently has little role in terminating the effects of bradykinin in the lung.