Premium
Angiotensin converting enzyme inhibitors potentiate the bronchoconstriction induced by substance P in the guinea‐pig
Author(s) -
Subissi Alessandro,
Guelfi Marco,
Criscuoli Marco
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb15837.x
Subject(s) - captopril , bronchoconstriction , propranolol , bradykinin , chemistry , pharmacology , angiotensin converting enzyme , prazosin , long term potentiation , angiotensin ii , capsaicin , endocrinology , enzyme inhibitor , medicine , blood pressure , antagonist , enzyme , biochemistry , receptor , asthma
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 ED 50 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.