Bradykinin-induced cough reflex markedly increases in patients with cough associated with captopril and enalapril.
We studied the effects of angiotensin converting enzyme (ACE) inhibitors on cough responses to bradykinin (BK), substance P (SP) and citric acid in a double blind, random study on 10 hypertensive patients receiving ACE inhibitors. Of these patients, five had reported cough with ACE inhibitors. Cough responses to citric acid were similar between patients with and without cough, and SP up to 10(-5) M did not cause cough in any of the subjects. BK caused cough at 13.4 +/- 1.2 (-log M) in 5 patients with cough associated with ACE inhibitors, but it did not cause cough at concentrations up to 10(-5) M in other 5 patients. One month after the withdrawal of ACE inhibitors, 5 patients were free from cough symptoms, and BK did not cause cough up to 10(-5) M in these patients, except for one who coughed at 10(-9) M, without changes in responses to citric acid. BK caused cough at 14.3 +/- 0.7 (-log M) although BK1-7, a major metabolite of BK by ACE, caused cough at 5.7 +/- 0.7 (-log M) in another 3 patients with cough associated with ACE inhibitor. These results suggest that impaired metabolism of BK induced by ACE inhibitors may relate to the manifestation of cough in hypertensive patients receiving ACE inhibitors.
Katsumata
U
U
First Department of Internal Medicine, Tohoku University, School of Medicine, Sendai, Japan.
Sekizawa
K
K
Ujiie
Y
Y
Sasaki
H
H
Takishima
T
T
D000328:Adult; D000336:Aerosols; D000368:Aged; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000009:adverse effects*; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced*; D004311:Double-Blind Method; D004656:Enalapril / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012018:Reflex / Q000187:drug effects*; D012129:Respiratory Function Tests; D013373:Substance P / Q000494:pharmacology
D000336:Aerosols; D002951:Citrates; D019343:Citric Acid; D013373:Substance P; D004656:Enalapril; D002216:Captopril; D001920:Bradykinin