Angiotensin converting enzyme inhibitors potentiate the bronchoconstriction induced by substance P in the guinea‐pig

Abstract

The effects of intravenous captopril and enalaprilic acid on the increase in pulmonary inflation pressure induced by different bronchoconstrictor agents were evaluated in the anaesthetized guinea‐pig. Captopril and enalaprilic acid (1.6–200 μg kg −1 ) enhanced dose‐dependently the bronchoconstriction (BC) induced by substance P. The threshold effective dose was 1.6 μg kg −1 and maximal potentiation over the control response was more than 400% for both agents. Enalaprilic acid was also assayed for serum and lung angiotensin converting enzyme (ACE) inhibition in anaesthetized guinea‐pigs. This drug produced a dose‐dependent inhibition of ACE in both tissues, with ED 50 s of 7.6 and 9.4 μg kg −1 , respectively: this inhibitory activity was positively correlated to substance P potentiation. Captopril (8–1000 μg kg −1 ) enhanced dose‐dependently the BC induced by capsaicin. The threshold effective dose was 40 μg kg −1 and maximal potentiation about 90%. Captopril (200–1000 μg kg −1 ) did not affect BC induced by bradykinin. However, this response was markedly enhanced (about 200%) by captopril 200 μg kg −1 in propranolol‐pretreated animals. Captopril and enalaprilic acid (200–1000 μg kg −1 ) slightly (20–40%) but significantly enhanced the BC induced by 5‐hydroxytryptamine. However, this response was potentiated to the same extent by a dose of prazosin, which produced a degree of hypotension similar to that observed after administration of the ACE inhibitors. In conclusion, ACE inhibitors potentiate the BC induced by substance P and, to a minor extent, that induced by capsaicin in the anaesthetized guinea‐pig. Potentiation of substance P is well correlated with ACE inhibition in guinea‐pig serum and lungs. These experimental results may offer a mechanistic interpretation of cough and bronchial hyperreactivity observed in patients receiving treatment with ACE inhibitors.