Bradykinin-mediated cough

Hypotension, in particular in combination with diuretics, is a well-known adverse reaction to ACE-inhibitors when used in patients with heart failure. Dry cough, possibly mediated by the accumulation of bradykinin, is also a well-known side-effect in 5-15% of the patients treated with an ACE-inhibitor. Impaired renal function may be worsened by ACE-inhibitors. Allergic reactions, sometimes rather intense, may be observed occasionally. In rare cases angioneurotic edema has been described. ACE inhibitors should be avoided in women who are likely... 

ACE) inhibitors, such as captopril. Up to 20% of these patients may develop a cough with ACE inhibitors. The cause is not known for certain, but it may be related to the accumulation in the lungs of bradykinin or other inflammatory mediators. Inhibiting ACE leads to an increase in bradykinin, which is normally broken down by this enzyme. The rash was originally attributed to a sulfhydryl group in captopril but is known to occur with other non-sutfhydryl-containing ACE-inhibitors. 

Cough In 5-20% of patients, ACE inhibitors induce a dry cough it usually is not dose-related, occurs more frequently in women than men, usually develops between 1 week and 6 months after initiation of therapy, and sometimes requires cessation of therapy. This adverse effect may be mediated by bradykinin, substance P, and/or prostaglandins. Thromboxane antagonism, aspirin, and iron supplementation reduce cough induced by ACE inhibitors. Once ACE inhibitors are stopped, the cough disappears, usually within 4 days. 

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Choudry NB, Fuller RW, Anderson N, Karlsson JA (1990) Separation of cough and reflex bron-choconstriction by inhaled local anaesthetics. Eur Respir J 3 579-583 Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Juhus D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411 957-962... 

C. Angioedema and cough associated with ACE inhibitors is thought to be mediated by bradykinin, which is nonnally broken down by the angiotensinconverting enzyme. However, it has also been reported with AR blockers, which do not alter bradykinin elimination. 

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