title: Captopril augments acetylcholine-induced bronchial smooth muscle contractions in vitro via kinin-dependent mechanisms.
abstract: Angiotensin converting enzyme (ACE) inhibitors therapy is aassociated with bothersome dry cough as an adverse effect. The mechanisms underlying this adverse effect are not clear. Therefore, influence of captopril (an ACE inhibitor) on acetylcholine (ACh)-induced bronchial smooth muscle contractions was investigated. Further, the mechanisms underlying the captopril-induced changes were also explored. In vitro contractions of rat bronchial smooth muscle to cumulative concentrations of ACh were recorded before and after exposure to captopril. Further, the involvement of kinin and inositol triphosphate (IP₃) pathways for captopril-induced alterations were explored. ACh produced concentration-dependent (5-500 µM) increase in bronchial smooth muscle contractions. Pre-treatment with captopril augmented the ACh-induced contractions at each concentration significantly. Pre-treatment with aprotinin (kinin synthesis inhibitor) or heparin (inositol triphosphate, IP₃-inhibitor), blocked the captopril-induced augmentation of bronchial smooth muscle contractions evoked by ACh. Further, captopril-induced augmentation was absent in calcium-free medium. These results suggest that captopril sensitizes bronchial smooth muscles to ACh-induced contractions. This sensitization may be responsible for dry cough associated with captopril therapy.
authors.forename: Naman
authors.initials: N
authors.lastname: Agrawal
authors.forename: Aparna
authors.initials: A
authors.lastname: Akella
authors.forename: Shripad B
authors.initials: SB
authors.lastname: Deshpande
mesh_terms: D000109:Acetylcholine / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D001986:Bronchial Spasm / Q000139:chemically induced; D002216:Captopril / Q000009:adverse effects*; D003371:Cough / Q000139:chemically induced; D004357:Drug Synergism; D007705:Kinins / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D002216:Captopril; D000109:Acetylcholine