STATE-OF-THE-ART PAPER
Cerebroprotection mediated by angiotensin II
A hypothesis supported by recent randomized clinical trials
Albert Fournier, MD*,
Franz H. Messerli, MD, FACC ,*,
Jean Michel Achard, MD and
Leonardo Fernandez, MD
* Hôpital Sud, Amiens Cedex I, France
Ochsner Clinic Foundation, New Orleans, Louisiana, USA
Limoges University, Limoges, France
Yale University, New Haven, Connecticut, USA
Manuscript received May 9, 2003;
revised manuscript received September 19, 2003,
accepted October 27, 2003.
* Reprint requests and correspondence: Dr. Franz H. Messerli, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, Louisiana 70121, USA.
fmesserli{at}aol.com
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.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | ALLHAT | = Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial | | ANBP2 | = Second Australian National Blood Pressure study | | ARB | = angiotensin II receptor blocker | | BP | = blood pressure | | CAPPP | = CAPtopril Prevention Project | | HOPE | = Heart Outcomes Prevention Evaluation study | | INSIGHT | = International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment | | LIFE | = Losartan Intervention For Endpoint study | | MRC | = Medical Research Council | | NORDIL | = NORdic DILtiazem study | | PATS | = Post-stroke Antihypertensive Treatment Study | | PROGRESS | = Perindopril Protection Against Recurrent Stroke | | SBP | = systolic blood pressure | | SCOPE | = Study on COgnition and Prognosis in the Elderly study | | SHEP | = Systolic Hypertension in the Elderly Program |
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