New Aspects of Ace Inhibition: Importance of ACE co-localization with angiotensin and bradykinin receptors
The beneficial effect of angiotensin-converting enzyme (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 (B2) receptor ‘crosstalk’, resulting in B2 receptor upregulation and/or more efficient activation of signal transduction pathways, as well as direct activation of bradykinin type 1 (B1) 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) (Ang-(1-7)), a metabolite of both angiotensin (Ang) I and II, that could act as an endogenous ACE inhibitor. The levels of Ang-(1-7) are increased during ACE inhibition, and most studies suggest that its hypotensive effects are mediated in a bradykinin-dependent manner.
|Publisher||Erasmus MC: University Medical Center Rotterdam|
|Promotor||Saxena, P.R. (Pramod Ranjan) , Danser, A.H.J. (Jan)|
|Sponsor||J.E. Jurriaanse Stichting, Sanofi-Synthelabo Recherche, GlaxoSmithKline B.V., Venlo, Türk Sosyal Kültürel Merkezi Vakfı (Stichting Turks Sociaal Cultureel Centrum Venlo), Dostluk Vakfı, Harlan Nederland B.V.|
|Keywords||ACE inhibitors, pharmacology|
Tom, B.. (2003, December 3). New Aspects of Ace Inhibition: Importance of ACE co-localization with angiotensin and bradykinin receptors. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/16169