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

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Abstract
1 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. 2 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 ED50 s of 7.6 and 9.4 μg kg−1, respectively: this inhibitory activity was positively correlated to substance P potentiation. 3 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%. 4 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. 5 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. 6 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.