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Comparative effects of the angiotensin II receptor blocker, telmisartan, and the angiotensin-converting enzyme inhibitor, ramipril, on cerebrovascular structure in spontaneously hypertensive rats

Dupuis, François; Atkinson, Jeffrey; Limiñana, Patrick; Chillon, Jean-Marc

doi: 10.1097/01.hjh.0000166848.95592.a5
Original papers: Brain circulation
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Objective Antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEIs) reverses cerebral arteriolar remodeling, thus restoring dilatation and hence the lower limit of cerebral blood flow (CBF) autoregulation (LLCBF). The objective of this study was to determine whether angiotensin II receptor AT1 blockers (ARBs) produce the same effect.

Design We examined the effects of treatment with an ARB [telmisartan (TEL), 1.93 ± 0.04 mg/kg per day] or an ACEI [ramipril (RAM), 1.00 ± 0.02 mg/kg per day] on the cerebral circulation in spontaneously hypertensive rats (SHR).

Methods Arteriolar pressure and diameter (cranial window) and CBF (laser Doppler) were measured during stepwise hypotensive hemorrhage, before and after deactivation (ethylenediamine tetraacetic acid), in untreated Wistar–Kyoto (WKY) rats and SHR untreated or treated for 3 months with TEL or RAM in the drinking water.

Results Treatment normalized arteriolar internal diameter (SHR, 38 ± 3 μm; TEL, 52 ± 2 μm; RAM, 50 ± 2 μm; WKY, 58 ± 4 μm), essentially by reversing eutrophic inward remodeling, and the LLCBF (SHR, 80 ± 11 mmHg; TEL, 60 ± 4 mmHg; RAM, 71 ± 6 mmHg; WKY, 57 ± 5 mmHg).

Conclusion The fact that the ARB (TEL) is as effective as an ACEI (RAM) in reversing cerebral arteriolar remodeling suggests that the cerebrovascular AT1 receptor is an underlying mechanism that promotes hypertensive eutrophic inward remodeling.

Cardiovascular Research Group, INSERM U684, Faculté de Pharmacie, Université Henri Poincaré-Nancy I, Nancy, France

Received 1 October, 2004

Revised 10 December, 2004

Accepted 4 January, 2005

Sponsorship: Supported by Boehringer Ingelheim Pharma Gmbh & Co. KG, The French Ministry of Education, Research and Technology (EA3448, Paris, France), The Lorraine Regional Development Committee (Metz, France), The Greater Nancy Urban Council (Nancy, France), Henri Poincaré University (Nancy, France) and the Pharmacolor Association (Nancy, France).

Correspondence and requests for reprints to Jeffrey Atkinson, Cardiovascular Research Group, INSERM U684, Faculté de Pharmacie, Université Henri Poincaré-Nancy I, 5 rue Albert Lebrun, 54000 Nancy, France. Tel: +33 3 83 68 22 62; fax: +33 3 83 68 23 01; e-mail: Jeffrey.Atkinson@pharma.uhp-nancy.fr

Part of this work was presented at the 8th Annual Congress of the French Pharmacological Society [Fund Clin Pharmacol 2004; 18:221] and the 5th Joint Meeting of the French and Chinese Pharmacological Societies, Beijing, 21–22 October 2004 [Acta Pharmacol Sin 2004; 25:1528].

© 2005 Lippincott Williams & Wilkins, Inc.