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.
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).
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.
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).
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].