Antioxidant treatment reduces matrix metalloproteinase-2-induced vascular changes in renovascular hypertension


Autoria(s): CASTRO, Michele M.; RIZZI, Elen; RODRIGUES, Gerson J.; CERON, Carla S.; BENDHACK, Lusiane M.; GERLACH, Raquel F.; TANUS-SANTOS, Jose E.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2009

Resumo

Mounting evidence indicates that structural and functional vascular changes associated with two-kidney, one-clip (2K-1C) hypertension result, at least in part, from altered activity of matrix metalloproteinases (MMPs). Because MMPs are upregulated by increased formation of reactive oxygen species (ROS), we hypothesized that antioxidant approaches could attenuate the increases in MMP-2 expression/activity and the vascular dysfunction and remodeling associated with 2K-1C hypertension. Sham-operated or 2K-1C hypertensive rats were treated with tempol 18 mg/kg/day or apocyanin 25 mg/kg/day (or vehicle). Systolic blood pressure was monitored weekly. After 8 weeks of treatment, aortic rings were isolated to assess endothelium-dependent and -independent relaxation. Quantitative morphometry of structural changes in the aortic wall was studied in hematoxylin/eosin sections. Aortic and systemic ROS levels were measured using dihydroethidine and thiobarbituric acid-reactive substances, respectively. Aortic MMP-2 levels and activity were determined by gelatin and in situ zymography, fluorimetry, and immunohistochemistry. Tempol and apocyanin attenuated 2K-1C hypertension (181 +/- 20.8 and 192 +/- 17.6 mm Hg, respectively, versus 213 +/- 18 mm Hg in hypertensive controls; both p<0.05) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Tempol, but not apocyanin (p>0.05), prevented the vascular remodeling found in 2K-1C rats (all p<0.01). Tempol was more effective than apocyanin in attenuating hypertension-induced increases in oxidative stress (both p<0.05), MMP-2 levels, and MMP-2 activity in hypertensive rats (all p<0.05). Our results suggest that antioxidant approaches decrease MMP-2 upregulation and attenuate the vascular dysfunction and remodeling during 2K-1C hypertension. (C) 2009 Elsevier Inc. All rights reserved.

FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo

CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico

Identificador

FREE RADICAL BIOLOGY AND MEDICINE, v.46, n.9, p.1298-1307, 2009

0891-5849

http://producao.usp.br/handle/BDPI/20038

10.1016/j.freeradbiomed.2009.02.011

http://dx.doi.org/10.1016/j.freeradbiomed.2009.02.011

Idioma(s)

eng

Publicador

ELSEVIER SCIENCE INC

Relação

Free Radical Biology and Medicine

Direitos

restrictedAccess

Copyright ELSEVIER SCIENCE INC

Palavras-Chave #Reactive oxygen species #Metalloproteinases #Vascular dysfunction #2K-1C hypertension #Antioxidants #Free radicals #SMOOTH-MUSCLE-CELLS #OXIDATIVE STRESS #REPERFUSION INJURY #TISSUE INHIBITOR #MMP-9 ACTIVITIES #NAD(P)H OXIDASE #RATS #PEROXYNITRITE #APOCYNIN #ACTIVATION #Biochemistry & Molecular Biology #Endocrinology & Metabolism
Tipo

article

original article

publishedVersion