Comparative study of effects of angiotensin II receptor antagonist, KD3-671, and angiotensin converting enzyme inhibitor, enalaprilat, on cough reflex in guinea pig

Angiotensin converting enzyme (ACE) inhibitor prevents the inactivation of bradykinin by inhibiting ACE activity, leading to side effects such as dry cough and angioedema. KD3-671 is a novel nonpeptide angiotensin II antagoni st which is expected to exhibit persistent hypotensive action without these side effects. In this study, we investigated the relationship between the pharmacokinetics and cough-inducing effect of this drug in guinea-pig, comp ared with that of an ACE inhibitor, enalaprilat. KD3-671 was not significan tly different from the vehicle treatment in the ability to induce coughing, whereas enalaprilat significantly enhanced coughing compared with the vehi cle treatment. Thus, as expected from its mechanism of pharmacological acti on, KD3-671 did not induce coughing. We suggest that the citric acid-induce d guinea pig coughing model will be useful in preclinical studies to examin e the effect of drug on pulmonary function.