The effects of captopril (SQ 14,225) on bradykinin-induced bronchoconstriction in the anesthetized guinea pig.
The effect of captopril (SQ 14,225) a potent inhibitor of angiotensin converting enzyme (ACE: kininase II) on the bronchoconstrictor response to bradykinin was studied in the anesthetized guinea pig. The i.v. administration of captopril caused a profound long lasting hypotension without affecting pulmonary resistance or dynamic compliance. Similarly, the i.v. administration of bradykinin caused small increases in pulmonary resistance and decreases in dynamic compliance which were not altered by the administration of captopril. However, after beta-receptor blockade with propranolol, bradykinin-induced changes in resistance and compliance were enhanced; additional captopril administration further potentiated the bradykinin effects. The prostaglandin synthetase inhibitor indomethacin antagonized the bradykinin-induced bronchoconstriction in beta-blocked animals and its potentiation by captopril. In the isolated perfused guinea pig lung, bradykinin caused a dose dependent release of a prostaglandin-like substance which was significantly increased by captopril and antagonized by indomethacin. These results suggest that bradykinin causes a prostaglandin-mediated bronchoconstriction. Captopril, a potent inhibitor of ACE, prevents the degradation of bradykinin thus potentiating the bradykinin-induced bronchoconstriction, an effect observed in intact animals only in the absence of pulmonary beta-receptor activation.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D001986:Bronchial Spasm / Q000139:chemically induced / Q000503:physiopathology*; D002216:Captopril / Q000494:pharmacology*; D004357:Drug Synergism; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors
D011392:Proline; D002216:Captopril; D011433:Propranolol; D001920:Bradykinin