title: Effect of chronic treatment with angiotensin type 1 receptor antagonists on striatal dopamine levels in normal rats and in a rat model of Parkinson's disease treated with L-DOPA.
abstract: Beneficial effects of angiotensin type-1 receptor (AT1) inhibition have been observed in a number of brain processes mediated by oxidative stress and neuroinflammation, including Parkinson's disease. However, important counterregulatory interactions between dopamine and angiotensin systems have recently been demonstrated in several peripheral tissues, and it is possible that a decrease in dopamine levels due to AT1 inhibition may interfere with neuroprotective strategies. The present experiments involving rats with normal dopaminergic innervation indicate that chronic treatment with the AT1 antagonist candesartan does not significantly affect striatal levels of dopamine, serotonin or metabolites, as does not significantly affect motor behavior, as evaluated by the rotarod test. Interestingly, chronic administration of candesartan to normal rats induced a marked increase in dopamine D1 and a decrease in dopamine D2 receptor expression. In a rat model of Parkinson's disease treated with L-DOPA, no differences in striatal dopamine and serotonin levels were observed between candesartan-treated rats and untreated, which suggests that chronic treatment with candesartan does not significantly affect the process of L-DOPA decarboxylation and dopamine release in Parkinson's disease patients. Candesartan did not induce any differences in the striatal expression of dopamine D1 and D2 and serotonin 5-HT1B receptors in 6ydroxydopamine-lesioned rats treated with L-DOPA. The results suggest that chronic treatment with AT1 antagonists as a neuroprotective strategy does not significantly affect striatal dopamine release or motor behavior. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.
authors: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors: Antonio
authors: A
authors: Dominguez-Meijide
authors: Begoña
authors: B
authors: Villar-Cheda
authors: Pablo
authors: P
authors: Garrido-Gil
authors: German
authors: G
authors: Sierrra-Paredes
authors: Maria J
authors: MJ
authors: Guerra
authors: Jose L
authors: JL
authors: Labandeira-Garcia
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018696:Neuroprotective Agents; D044302:Receptor, Serotonin, 5-HT1B; D011954:Receptors, Dopamine; D013777:Tetrazoles; D012701:Serotonin; D007980:Levodopa; D016627:Oxidopamine; C081643:candesartan; D004298:Dopamine
keywords: 3,4-dihydroxyphenylacetic acid; 5-HIAA; 5-HT; 6-OHDA; 6-hydroxydopamine; AII; AT1; AT2; AUC; Angiotensin; Candesartan; DOPAC; HPLC; HVA; L-3,4-dihydroxyphenylalanine methyl ester hydrochloride; Neuroprotection; ORP; Parkinson; RAS; SEM; Serotonin; TH; WB; Western blot analysis; angiotensin II; angiotensin type-1 receptor; angiotensin type-2 receptor; area under the curve; high performance liquid chromatograph; homovanillic acid; l-DOPA; metabolite 5-hydroxyindolacetic acid; overall rod performance; renin-angiotensin system; serotonin; standard error of the mean; tyrosine hydroxylase