Angiotensin converting enzyme (ACE) inhibitor-induced cough and substance P.
BACKGROUND
Angiotensin converting enzyme (ACE) inhibitors cause coughing in 5-10% of patients, but the exact mechanisms of this effect are still unclear. In the airways ACE degrades substance P so the cough mechanism may be related to this peptide.


METHODS
Nine patients who developed a cough and five patients who did not develop a cough when taking the ACE inhibitor enalapril (2.5 or 5.0 mg/day) for hypertension were enrolled in the study. No subjects had respiratory disease and the respiratory function of all subjects was normal. One month after stopping enalapril, inhalation of hypertonic saline (4%) was performed using an ultrasonic nebuliser for 15-30 minutes to induce sputum. The concentration of substance P in the sputum sample was measured by radioimmunoassay. In four of the nine cases with a cough enalapril was given again for 1-2 weeks and the concentration of substance P in the induced sputum was again measured.


RESULTS
One month after stopping enalapril the mean (SE) concentration of substance P in the sputum of the group with a cough was 16.6 (3.0) fmol/ml, significantly higher than that in the subjects without a cough (0.9 (0.5) fmol/ml). All four subjects in the group with a cough who were given a repeat dose of enalapril developed a cough again, but the concentrations of substance P in the induced sputum while taking enalapril (17.9 (3.2) fmol/ml) were similar to the values whilst off enalapril (20.0 (2.5) fmol/ml).


CONCLUSIONS
The mechanisms of ACE inhibitor-induced coughing may involve substance P mediated airway priming. However, the final triggering of the ACE inhibitor-induced coughing is unlikely to be due to this peptide.
Tomaki
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Japan.
Ichinose
M
M
Miura
M
M
Hirayama
Y
Y
Kageyama
N
N
Yamauchi
H
H
Shirato
K
K
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D003371:Cough / Q000139:chemically induced* / Q000378:metabolism; D004656:Enalapril / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000737:chemistry; D013373:Substance P / Q000032:analysis*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D013373:Substance P; D004656:Enalapril