Rey, PabloLópez-Real, A.Sánchez Iglesias, SofíaMuñoz, AnaSoto-Otero, RamónLabandeira García, José Luis2024-02-072024-02-072007Neurobiology of Aging, Volume 28, Issue 4, 2007, Pages 555-567http://hdl.handle.net/10347/32468Angiotensin 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.engCC BY-NC-NDhttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.glAngiotensinBasal gangliaDopamineNeuroprotectionNAD(P)H-oxidaseParkinson's diseaseOxidative stress6-Hydroxydopaminejournal article10.1016/j.neurobiolaging.2006.02.018open access