title: Key developments in renin-angiotensin-aldosterone system inhibition.
abstract: The renin-angiotensin-aldosterone system (RAAS) was initially thought to be fairly simple. However, this idea has been challenged following the development of RAAS blockers, including renin inhibitors, angiotensin-converting-enzyme (ACE) inhibitors, type 1 angiotensin II (AT(1))-receptor blockers and mineralocorticoid-receptor antagonists. Consequently, new RAAS components and pathways that might contribute to the effectiveness of these drugs and/or their adverse effects have been identified. For example, an increase in renin levels during RAAS blockade might result in harmful effects via stimulation of the prorenin receptor (PRR), and prorenin-the inactive precursor of renin-might gain enzymatic activity on PRR binding. The increase in angiotensin II levels that occurs during AT(1)-receptor blockade might result in beneficial effects via stimulation of type 2 angiotensin II receptors. Moreover, angiotensin 1-7 levels increase during ACE inhibition and AT(1)-receptor blockade, resulting in Mas receptor activation and the induction of cardioprotective and renoprotective effects, including stimulation of tissue repair by stem cells. Finally, a role of angiotensin II in sodium and potassium handling in the distal nephron has been identified. This finding is likely to have important implications for understanding the effects of RAAS inhibition on whole body sodium and potassium balance.
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sevá Pessôa
authors.forename: Nils
authors.initials: N
authors.lastname: van der Lubbe
authors.forename: Koen
authors.initials: K
authors.lastname: Verdonk
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Roks
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D000092502:Renin Inhibitors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D000092502:Renin Inhibitors