Bradykinin, angiotensin-(1-7), and ACE inhibitors: how do they interact?
The beneficial effect of ACE inhibitors in hypertension and heart failure may relate, at least in part, to their capacity to interfere with bradykinin metabolism. In addition, recent studies have provided evidence for bradykinin-potentiating effects of ACE inhibitors that are independent of bradykinin hydrolysis, i.e. ACE-bradykinin type 2 (B(2)) receptor 'cross-talk', resulting in B(2) receptor upregulation and/or more efficient activation of signal transduction pathways, as well as direct activation of bradykinin type 1 receptors by ACE inhibitors. This review critically reviews the current evidence for hydrolysis-independent bradykinin potentiation by ACE inhibitors, evaluating not only the many studies that have been performed with ACE-resistant bradykinin analogues, but also paying attention to angiotensin-(1-7), a metabolite of both angiotensin I and II, that could act as an endogenous ACE inhibitor. The levels of angiotensin-(1-7) are increased during ACE inhibition, and most studies suggest that its hypotensive effects are mediated in a bradykinin-dependent manner.
Tom
Beril
B
Department of Pharmacology, Room EE1418b, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Dendorfer
Andreas
A
Danser
A H Jan
AH
D000803:Angiotensin I / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C118790:angiotensin I (1-7); D001920:Bradykinin