IngentaConnect Ramipril prevents extracellular matrix accumulation in cerebral m...

Authors: Liebetrau, Martin¹; Burggraf, Dorothe²; Büscher, Christine²; Linz, Wolfgang³; Hamann, Gerhard F.¹

Source: Neurological Research, Volume 27, Number 5, July 2005 , pp. 477-482(6)

Abstract:

Objectives: The stroke-prone spontaneously hypertensive rat is a genetic model of severe hypertension with secondary vascular alterations. The aim of this study was to determine the influence of chronic hypertension and ramipril treatment on the extracellular matrix in the cerebral microvasculature.

Methods: The study consisted of three groups: six normotensive Wistar rats, six untreated spontaneously hypertensive rats, and six hypertensive rats treated with an antihypertensive dose of ramipril (1 mg kg^&minus1 day^-1) for 6 months. Alterations in the extracellular matrix were examined by western blot, immunohistochemistry, and immunofluorescence using an antibody against collagen type IV.

Results: Western blotting showed a reduction of the total amount of collagen type IV by 50% in the ramipril group compared with the untreated hypertensive group (51.0 ± 9.3% reduction, p=0.0004). Compared with the untreated hypertensive rats, ramipril treatment prevented a loss of vessel density in the cortex (23.4 ±1.0 versus 20.4 ± 2.0, p<0.0001) and revealed a reduction of the amount of collagen per vessel (0.54 ± 0.04 versus 0.60 ± 0.08, p=0.037). The ratio between the vessel wall and the lumen (0.69 ± 0.08 versus 1.31 ± 0.13) and the relative collagen intensity was lowered in the ramipril group (18.1 ± 4.7% reduction, p<0.0001). Using these methods the ramipril group showed similar results than the normotensive group.

Discussion: Ramipril treatment completely prevented these hypertensive vascular changes. These results may stimulate a therapeutic approach with angiotensin converting enzyme inhibition in human hypertensive small vessel disease.

Keywords: ACE INHIBITION; COLLAGEN; EXTRACELLULAR MATRIX; IMMUNOHISTOCHEMISTRY; SPONTANEOUSLY HYPERTENSIVE RATS

Document Type: Research article

DOI: 10.1179/016164105X49256

Affiliations: 1: Department of Neurology, Dr. Horst Schmidt Klinik, Ludwig-Erhard Str. 100, 65199 Wiesbaden, Germany 2: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany 3: Aventis Pharma, DG Cardiovascular, Frankfurt/Main, Germany

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Ramipril prevents extracellular matrix accumulation in cerebral microvessels