Volume 1, Number 1, March 2000

ACE inhibitors, angiotensin receptor antagonists and bradykinin
Michael Schachter

Soon after the introduction of angiotensin-converting enzyme inhibitors (ACE-I), it became clear that the drugs were not specific for angiotensin I (Ang I), but also inhibited the breakdown of bradykinin (BK) and substance P. Moreover, the affinity of ACE for BK is much higher than for Ang I at both active sites of the enzyme. There has been great interest in trying to establish whether BK plays an important role in the therapeutic effects of ACE-I. It is now generally believed that BK is probably the major contributor to two of the side-effects characteristic of ACE-I - cough and angioedema.
BK has a variety of biological effects that can be categorised as pro-inflammatory (mostly involving the BK₁ receptor subtype) and vasodilatory (involving predominantly BK₂ receptors). Activation of endothelial BK₂ receptors leads to increased synthesis of nitric oxide (NO) and release of prostacyclin; it is thus plausible that some of the vasodilator response to ACE inhibition may be mediated by increased generation of kinins and NO. There is also evidence that ACE-I may have a direct effect by preventing sequestration and inactivation of the BK₂ receptor and by re-activating the receptor in BK-treated cells.
This paper reviews the currently available published data in both animal and human studies on the interactions of ACE and BK and the potential role of kinins in the response to ACE inhibition.

JRAAS 2000;1:27-29.

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