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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Cardiopatía hipertensiva > DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista >

Overexpression of Bax protein and enhanced apoptosis in the left ventricle of spontaneously hypertensive rats: effects of AT1 blockade with losartan
Authors: Fortuño, M.A. (María Antonia)
Ravassa, S. (Susana)
Etayo, J.C. (Juan Carlos)
Diez, J. (Javier)
Keywords: Angiotensin II
Apoptosis
Bax
Bcl-2
Losartan
Rats, inbred SHR
Issue Date: 1998
Publisher: American heart association
Publisher version: http://dx.doi.org/10.1161/​01.HYP.32.2.280
ISSN: 0194-911X
Citation: Fortuño MA, Ravassa S, Etayo JC, Diez J. Overexpression of Bax Protein and Enhanced Apoptosis in the Left Ventricle of Spontaneously Hypertensive Rats. Hypertension 1998 Aug;32(2):280-286.
Abstract
An association of increased apoptosis with overactivity of the local angiotensin-converting enzyme has been reported in cells from the left ventricle of adult rats with spontaneous hypertension (SHR). To gain insight into the regulation of cardiac apoptosis in arterial hypertension, we investigated the expression of the proteins Bcl-2 (an inhibitor of apoptosis) and Bax (an inducer of apoptosis) in the left ventricle of 30-week-old normotensive Wistar-Kyoto rats (WKY), SHR, and SHR treated with the angiotensin II type 1 receptor (AT1) antagonist losartan (20 mg x kg(-1) x d(-1)) during 14 weeks before death. The density of apoptotic cells was assessed by direct immunoperoxidase detection of biotin-labeled deoxyuridin nucleotides. The expression of Bcl-2 and Bax was assessed by Western blot analysis. Compared with WKY, untreated SHR exhibited increased (P<0.05) apoptosis, increased (P<0.01) Bax, and similar Bcl-2. The Bcl-2/Bax ratio (an inverse index of cell susceptibility to apoptosis) was lower (P<0.05) in untreated SHR than in WKY. The chronic administration of losartan was associated with the normalization of apoptosis, Bax expression, and the Bcl-2/Bax ratio in treated SHR. No changes in the expression of Bcl-2 were observed in these rats after treatment. No significant changes in the apoptotic density were observed between treated SHR with normal blood pressure and treated SHR with abnormally high blood pressure at the end of the treatment period. These results suggest that an association exists between increased apoptosis and overexpression of Bax oncoprotein in cells from the left ventricle of adult SHR. Chronic blockade of AT1 receptors prevents Bax overexpression and normalizes apoptosis in the left ventricle of SHR independently of its hemodynamic effect. On the basis of our findings, it can be proposed that the interaction of angiotensin II with its AT1 receptors may participate in the stimulation of Bax protein, which in turn renders cells from the left ventricle of SHR more susceptible to apoptosis.
Permanent link: http://hdl.handle.net/10171/20236
Appears in Collections:DA - CIMA - Servicios de apoyo - Biobanco - Artículos de revista
DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista

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