Synergistic potentiation by captopril and propranolol of bradykinin-induced bronchoconstriction in the guinea-pig.
1. Captopril (30 or 100 micrograms/kg intravenous (i.v.] in anaesthetized artificially ventilated guinea-pigs potentiated bronchoconstrictor responses to bradykinin, but not those to histamine or the thromboxane A2-mimetic U46619. 2. Propranolol (5 mg/kg, i.v.) potentiated bradykinin-induced broncho-constriction. 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 A2 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 broncho-constriction in the guinea-pig indirectly, by release of eicosanoids. Thromboxane A2 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 beta-adrenoceptors. Kininase I, in contrast to kininase II apparently has little role in terminating the effects of bradykinin in the lung.
Lau
W A
WA
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Rechtman
M P
MP
Boura
A L
AL
King
R G
RG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004357:Drug Synergism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D001095:Arachidonic Acids; D001713:Biphenyl Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C046926:AH 23848; D006632:Histamine; D002216:Captopril; D011433:Propranolol; D001920:Bradykinin