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Entacapone protects from angiotensin II-induced inflammation and renal injury

Item Type:Article
Title:Entacapone protects from angiotensin II-induced inflammation and renal injury
Creators Name:Helkamaa, T. and Finckenberg, P. and Louhelainen, M. and Merasto, S. and Rauhala, P. and Lapatto, R. and Cheng, Z.J. and Reenilae, I. and Maennistoe, P. and Mueller, D.N. and Luft, F.C. and Mervaala, E.M.
Abstract:OBJECTIVES AND DESIGN: Angiotensin II (Ang II)-induced renal damage is associated with perivascular inflammation and increased oxidative stress. We tested the hypothesis whether entacapone, a catechol-O-methyltransferase (COMT) inhibitor exerting antioxidative and anti-inflammatory properties, protects against the Ang II-induced inflammatory response and end-organ damage. METHODS: Samples from double-transgenic rats harbouring human renin and human angiotensinogen genes (dTGR) and normotensive Sprague-Dawley rats (SD) were assessed by light microscopy, immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR), and high pressure liquid chromatography. The effects of entacapone treatment for 3 weeks were examined in dTGR and SD. RESULTS: Entacapone completely prevented cardiovascular mortality and decreased albuminuria by 85% in dTGR. Entacapone ameliorated Ang II-induced vascular and glomerular damage, leucocyte infiltration, and intercellular adhesion molecule-1 (ICAM-1) overexpression in the kidneys. Serum 8-isoprostane concentration, as well as renal nitrotyrosine and 8-hydroxydeoxyguanosine expressions, all markers of oxidative stress, were markedly increased in dTGR and normalized by entacapone. Entacapone also decreased p22phox mRNA expression in the kidney. COMT expression was increased by 500% locally in the renal vascular wall in dTGR; however, COMT activity in the whole kidney remained unchanged. Urinary dopamine excretion, a marker of renal dopaminergic tone, was decreased by 50% in untreated dTGR. Even though entacapone decreased renal COMT activity by 40%, the renal dopaminergic tone remained unchanged in entacapone-treated dTGR. CONCLUSION: Our findings suggest that entacapone provides protection against Ang II-induced renal damage through antioxidative and anti-inflammatory mechanisms, rather than by COMT inhibition-induced changes in renal dopaminergic tone.
Keywords:Catechol-O-methyltransferase, Dopamine, Catecholamines, Angiotensin II, Albuminuria, Entacapone
Source:Journal of Hypertension
Publisher:Lippincott Williams & Wilkins
Page Range:2353-2363
Date:1 January 2003
Official Publication:https://doi.org/10.1097/01.hjh.0000098146.70956.9d
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