HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fournier, A. Articles by Fernandez, L. Search for Related Content PubMed PubMed Citation Articles by Fournier, A. Articles by Fernandez, L.

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.

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

This article has been cited by other articles:

				F. H. Messerli Cerebroprotection by Hypertension in Ischemic Stroke: The Crumbling of a Hypothesis Circulation, June 12, 2007; 115(23): 2907 - 2908. [Full Text] [PDF]

				N. Chitravas, H. M. Dewey, M. B. Nicol, D. L. Harding, D. C. Pearce, and A. G. Thrift Is prestroke use of angiotensin-converting enzyme inhibitors associated with better outcome? Neurology, May 15, 2007; 68(20): 1687 - 1693. [Abstract] [Full Text] [PDF]

				S. G. Tsouli, E. N. Liberopoulos, D. N. Kiortsis, D. P. Mikhailidis, and M. S. Elisaf Combined Treatment With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers: A Review of the Current Evidence Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2006; 11(1): 1 - 15. [Abstract] [PDF]

				J.-M. Vincent, Y. W. Kwan, S. Lung Chan, C. Perrin-Sarrado, J. Atkinson, and J.-M. Chillon Constrictor and Dilator Effects of Angiotensin II on Cerebral Arterioles Stroke, December 1, 2005; 36(12): 2691 - 2695. [Abstract] [Full Text] [PDF]

				B. Ovbiagele, C. S. Kidwell, S. Starkman, S. L. Selco, V. Rajajee, T. Razinia, and J. L. Saver Angiotensin 2 type 2 receptor activity and ischemic stroke severity Neurology, September 27, 2005; 65(6): 851 - 854. [Abstract] [Full Text] [PDF]

				The National Heart, Lung, and Blood Institute Work Major Clinical Trials of Hypertension: What Should Be Done Next? Hypertension, July 1, 2005; 46(1): 1 - 6. [Abstract] [Full Text] [PDF]

				T. E. Strandberg Editorial Comment: Secondary Prevention of Stroke Is Important: But All Hypertensive Drugs Are Not Created Equal? Stroke, June 1, 2005; 36(6): 1225 - 1226. [Full Text] [PDF]

				B. Williams Recent hypertension trials: Implications and controversies J. Am. Coll. Cardiol., March 15, 2005; 45(6): 813 - 827. [Abstract] [Full Text] [PDF]

				J. K. Ghali Cerebroprotection mediated by angiotensin II J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2097 - 2097. [Full Text] [PDF]

				F. H. Messerli and A. Fournier Reply J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2097 - 2098. [Full Text] [PDF]

				F. H. Messerli and A. Fournier Re: Lawes et al: Blood Pressure and Stroke Stroke, October 1, 2004; 35(10): 2238 - 2238. [Full Text] [PDF]

				V. Papademetriou, C. Farsang, D. Elmfeldt, A. Hofman, H. Lithell, B. Olofsson, I. Skoog, P. Trenkwalder, A. Zanchetti, and for the SCOPE Study Group Stroke prevention with the angiotensin II type 1-receptor blocker candesartan in elderly patients with isolated systolic hypertension: The study on cognition and prognosis in the elderly (SCOPE) J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1175 - 1180. [Abstract] [Full Text] [PDF]