The influence of inhaled furosemide on adverse effects of ACE-inhibitors in airways.
BACKGROUND
A persistent, chronic dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors therapy. The mechanism of this respiratory adverse effect is related to the inhibition of ACE and the accumulation of bradykinin, substance P, prostanoids and inflammatory neuropeptides in the airways.


OBJECTIVE
The aim of this study was to follow the relationship between 15-days administration of enalapril and the defence reflexes of the airways of experimental animals and possibility of pharmacological restriction with inhaled furosemide.


METHODS
From the defence reflexes of the airways the changes of the parameters of a mechanically induced cough in nonanaesthetized cats were measured. The reactivity of the smooth muscle of the airways to the bronchoconstrictor mediator was evaluated by in vitro method. The enalapril was administered for 15-days in the dosage of 5 mg/kg b.w. p.o., inhaled furosemide for 15-days in the dosage 10 mg/kg b.w.


RESULTS
The results suggested that long-lasting administration of enalapril resulted in a significant increase of measured cough parameters and increased reactivity of tracheal smooth muscle to the histamine. The reactivity of the lung smooth muscle was not influenced significantly after enalapril treatment. Inhaled furosemide administered with enalapril significantly decreased the enalapril induced cough and decreased enalapril potentiated reactivity of the tracheal smooth muscle to the histamine.


CONCLUSIONS
The results showed the protective effect of inhaled furosemide against the respiratory adverse effects induced by ACE-inhibitors administration.
Franova
S
S
Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. franova@jfmed.uniba.sk
D000280:Administration, Inhalation; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D000818:Animals; D002415:Cats; D003371:Cough / Q000139:chemically induced; D004232:Diuretics / Q000008:administration & dosage*; D004656:Enalapril / Q000009:adverse effects*; D005665:Furosemide / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D014132:Trachea / Q000187:drug effects* / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D004656:Enalapril; D005665:Furosemide