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

作者：Rey P; Lopez Real A; Sanchez Iglesias S; Munoz A; Soto Otero R; Labandeira Garcia J L^*

来源：Neurobiology of Aging, 2007, 28(4): 555-567.

DOI：10.1016/j.neurobiolaging.2006.02.018

• angiotensin
• basal ganglia
• dopamine
• neuroprotection
• NAD(P)H-oxidase
• Parkinson's disease
• oxidative stress
• 6-hydroxydopamine

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 (AT(1)) 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 AT(1) 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 AT, receptors, in increasing the oxidative damage of dopaminergic cells, and treatment with AT, antagonists may reduce the progression of Parkinson's disease.

• 出版日期2007-4