Unraveling the Complexities of the Renin-Angiotensin System: From ACE to renin inhibition
Ontrafeling van de complexiteit van het Renine-angiotensine systeem: Van ACE tot renine remming
Ang II generated at tissue sites stimulates both AT1 and AT2 receptors. This local generation depends largely on angiotensinogen and renin and/or prorenin taken up from blood, the latter uptake possibly involving the recently discovered (pro)renin receptor. ACE is generated locally, and appears to be the main, if not the only, Ang II-generating enzyme. Ang II has a whole range of metabolites, the most important of which are Ang-(1-7), Ang III and Ang IV. The enzymes generating these metabolites, including ACE2, have recently been characterized, as well as their putative (non- AT1/AT2) receptors, like the Mas and AT4 receptor. Stimulation of AT2 receptors most likely contributes to the benefi cial effect of RAS blockers, in particular during AT1 receptor antagonism. These receptors are upregulated under pathophysiological conditions, and are generally believed to counteract the effects of AT1 receptor stimulation. However, not all studies agree on this aspect, and thus it remains to be seen how the effect of drugs that completely suppress the RAS, i.e., renin inhibitors, compare to those that allow/require AT2 receptor stimulation, like ACE inhibitors and AT1 receptor antagonists.
|A.H.J. Danser (Jan)|
|Erasmus University Rotterdam|
|Netherlands Heart Foundation, J.E. Jurriaanse Stichting, Data Sciences International, Uno Roestvaststaal B.V., Harlan Netherlands B.V., Sanofi -Aventis Netherlands B.V.|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
van Esch, J.H.M. (2008, June 4). Unraveling the Complexities of the Renin-Angiotensin System: From ACE to renin inhibition. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/13132