ACE-inhibitors and defence reflexes of the airways.
The group of angiotensin-converting enzyme (ACE) inhibitors is one of the drugs of choice for the treatment of hypertension and congestive heart disease. However, it has been reported that in some of patients ACE-inhibitors induce hyperreactivity of the airways with occurrence of a persistent dry cough, dyspnoe and wheezing. We supposed that the mechanism of these hyperreactivity is connected to accumulation of bradykinin, tachykinins and other inflammatory mediators in the airways. Increased local concentration of inflammatory neuropeptides stimulates bronchial C fibres and rapidly adapting receptors and provoke the cough reflex. Inflammatory processes in the airways could be followed by contraction of airway smooth muscle. In this study, our aim was to measure the changes of the number and intensity of mechanical induced cough in cats, which were treated for days with enalapril (5 mg/kg b.w.). After 15 days of treatment the reactivity of the lung and tracheal smooth muscles to the bronchoconstrictor mediator histamine was estimated. As to our finding 15 days of administration of enalapril results in significant increase of cough parameters measured with a more significant sensitivity of the laryngopharyngeal part. In the experimental animals we observed increased reactivity of bronchial smooth muscle to histamine after 15 days of enalapril treatment. The reactivity of the lung smooth muscle to the histamine was not significantly changed. These results confirmed the increased cough sensitivity and increased bronchial reactivity after enalapril treatment. These experimental animal model may be useful for the investigation of the pharmacological minimization of respiratory adverse effect of ACE-inhibitors.
Franová
S
S
Department of Pharmacology, Jessenius Medical Faculty, Comenius University, Martin, Slovakia. franova@doctorjfmed.uniba.sk
Nosál'ová
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002415:Cats; D003371:Cough / Q000139:chemically induced* / Q000503:physiopathology; D004656:Enalapril / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D006632:Histamine