Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergic neurons

Rey, P.; Lopez-Real, A.; Sanchez-Iglesias, S.; Muñoz, A.; Soto-Otero, R.; Labandeira-Garcia, J.L.

doi:10.1016/j.neurobiolaging.2006.02.018

« Previous Next »Neurobiology of Aging
Volume 28, Issue 4 , Pages 555-567, April 2007

Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergic neurons

P. Rey
- Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
A. Lopez-Real
- Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
S. Sanchez-Iglesias
- Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
A. Muñoz
- Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
R. Soto-Otero
- Laboratory of Neurochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
J.L. Labandeira-Garcia
- Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
- Corresponding author at: Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. Tel.: +34 981563100; fax: +34 981547078.

Received 8 March 2005; received in revised form 20 February 2006; accepted 27 February 2006. published online 18 April 2006.

Abstract

Angiotensin II activates (via type 1 receptors) NAD(P)H-dependent oxidases, which are a major source of superoxide, and is relevant in the pathogenesis of several cardiovascular diseases and certain degenerative changes associated with ageing. Given that there is a brain renin–angiotensin system and that oxidative stress is a key contributor to Parkinson's disease, we investigated the effects of angiotensin II and angiotensin type 1 (AT₁) receptor antagonists in the 6-hydroxydopamine model of Parkinson's disease. Rats subjected to intraventricular injection of 6-hydroxydopamine showed bilateral reduction in the number of dopaminergic neurons and terminals. Injection of angiotensin alone did not induce any significant effect. However, angiotensin increased the toxic effect of 6-hydroxydopamine. Rats treated with the AT₁ receptor antagonist ZD 7155 and then 6-hydroxydopamine (with or without exogenous administration of angiotensin) showed a significant reduction in 6-hydroxydopamine-induced oxidative stress (lipid peroxidation and protein oxidation) and dopaminergic degeneration. Dopaminergic degeneration was also reduced by the NAD(P)H inhibitor apocynin. Angiotensin may play a pivotal role, via AT₁ receptors, in increasing the oxidative damage of dopaminergic cells, and treatment with AT₁ antagonists may reduce the progression of Parkinson's disease.

Keywords: Angiotensin, Basal ganglia, Dopamine, Neuroprotection, NAD(P)H-oxidase, Parkinson's disease, Oxidative stress, 6-Hydroxydopamine