Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials.
Based on the Medical Research Council study, Brown and Brown hypothesized in 1986 that angiotensin II could protect against strokes by causing vasoconstriction of the proximal cerebral arteries, thereby preventing Charcot-Bouchard aneurysms from rupturing. In light of this hypothesis, we evaluated the cerebroprotective effects of various drug classes in recent double-blinded, prospective, randomized trials, such as SHEP, PATS, CAPPP, HOPE, PROGRESS, INSIGHT, NORDIL, LIFE, SCOPE, ANBP2, and ALLHAT. Drugs that activate the AT2 receptors, such as diuretics, calcium antagonists, and angiotensin receptor blockers (ARBs), were consistently more beneficial for stroke reduction than drugs devoid of such activation, such as beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, despite an equal fall in arterial pressure (at least in patients with a low incidence of cardiac complications). These clinical and epidemiologic observations are supported by experimental data documenting greater cerebroprotection with ARBs (which increase angiotensin II levels and stimulate the AT2 receptors) than with ACE inhibitors. Stroke is the most devastating consequence of hypertensive cardiovascular disease, and our hypothesis of cerebroprotection by AT2 receptor activation should be tested by a head-to-head comparison of an ARB with an ACE inhibitor.
Fournier
Albert
A
Hôpital Sud, Amiens Cedex I, France.
Messerli
Franz H
FH
Achard
Jean Michel
JM
Fernandez
Leonardo
L
D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*
D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004232:Diuretics