Are angiotensin receptor blockers neuroprotective?
Stroke is one of the leading causes of invalidism and death in the industrialized world. Among others, the renin- angiotensin system (RAS) has been implicated in the pathogenesis and outcome of ischemic events, including stroke. Angiotensin II (Ang II), the major effector peptide of the RAS, exerts most of its well-defined physiologic and pathophysiologic actions, including those on the central and peripheral nervous system, through its Ang II type 1 (AT1) receptor subtype. This receptor not only contributes to stroke-related pathologic mechanisms (eg, hypertension, atherothrombosis, and cardiac hypertrophy) but also may be involved in postischemic damage to the brain. However, it has also been demonstrated that Ang II, via its AT2 receptor subtype, accelerates neuronal tissue regeneration after injury. In this article, we review the experimental evidence supporting the notion that blockade of brain AT1 receptors can be beneficial with respect to stroke incidence and outcome. We further delineate how AT2 receptors could be involved in neuronal regeneration following brain injury, such as stroke. In doing so, we also attempt to shed some light on the mechanisms by which AT1 receptor blockers, which leave the AT2 receptor unopposed, might exert protective actions in brain ischemia.
Thöne-Reineke
Christa
C
Center for Cardiovascular Research (CCR)/Institut für Pharmakologie und Toxikologie, Campus Charité Mitte Charité--Universitätsmedizin Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany.
Zimmermann
Mathias
M
Neumann
Christian
C
Krikov
Maxim
M
Li
Jun
J
Gerova
Nadja
N
Unger
Thomas
T
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002545:Brain Ischemia / Q000503:physiopathology*; D002455:Cell Division; D006801:Humans; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C077793:candesartan cilexetil