title: Is the angiotensin II Type 2 receptor cerebroprotective?
abstract: Most of the deleterious effects of angiotensin II (Ang II) on blood pressure (BP), cardiovascular remodeling, and atherosclerosis are mediated by Ang II type 1 (AT1)-receptor activation. This explains why Ang-II-decreasing or blocking drugs have been successful in decreasing global cardiovascular morbimortality in patients with cardiac complications. However, in primary or secondary stroke prevention trials in patients with low cardiac risk, b-blockers and angiotensin-converting enzyme inhibitors (ACEIs), which decrease Ang II formation, seem to be less protective than thiazides and dihydropyridines, which increase Ang II. When compared with a beta-blocker, an Ang II-increasing AT1-receptor blocker better protects against stroke but not against cardiac events, whereas an ACEI gives the same protection against both cardiac and cerebral events. This dissociation between blood-pressure-independent cardiac and cerebral protection between b-blockers or ACEIs versus AT1-blockers in patients with low cardiac risk can be best explained if, besides the beneficial vascular effect of AT1-receptor blunting, there is evidence of a beneficial effect of non-AT1-receptor activation. In this review, we present experimental evidence for AT2- and AT4-receptor-mediated brain-anti-ischemic mechanisms and propose a direct comparison of AT1-blockers with ACEIs to prove the clinical effectiveness of non-AT1-mediated mechanisms in stroke prevention, particularly in patients with a higher risk for stroke than for cardiac complications.
authors.affiliation: Service de Néphrologie, CHU SUD, Avenue René Laënnec, 80054 Amiens 1, France. fournier.albert@chu-amiens.fr
authors.forename: Albert
authors.initials: A
authors.lastname: Fournier
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Achard
authors.forename: Florent
authors.initials: F
authors.lastname: Boutitie
authors.forename: Hakim
authors.initials: H
authors.lastname: Mazouz
authors.forename: Janette
authors.initials: J
authors.lastname: Mansour
authors.forename: Roxana
authors.initials: R
authors.lastname: Oprisiu
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fernandez
authors.forename: Franz
authors.initials: F
authors.lastname: Messerli
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D044140:Receptor, Angiotensin, Type 1 / Q000627:therapeutic use; D044139:Receptor, Angiotensin, Type 2 / Q000627:therapeutic use*; D011945:Receptors, Angiotensin / Q000627:therapeutic use; D020521:Stroke / Q000503:physiopathology / Q000517:prevention & control
chemical_list: C090830:AT4 receptor; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin