title: Resveratrol improves vasoprotective effects of captopril on aortic remodeling and fibrosis triggered by renovascular hypertension.
abstract: BACKGROUND
  Renin-angiotensin system triggers vascular remodeling and fibrosis during the renovascular hypertensive two-kidney, one-clip (2K1C) model by oxidative-stress-mediated mechanisms. Thus, we hypothesized that the chronic treatment with the polyphenolic antioxidant resveratrol would improve the vasoprotective effects promoted by the chronic treatment with the angiotensin-converting enzyme inhibitor (ACEi) captopril in 2K1C hypertensive rats. Our main objective was to evaluate the effects of the combined treatment with resveratrol and captopril on vascular remodeling and fibrosis in 2K1C rats.
  
  
  METHODS
  Male Wistar rats underwent to unilateral renal stenosis by 2K1C Goldblatt model. Six weeks after surgery, rat systolic blood pressure (SBP) was measured by indirect tail-cuff plethysmography. 2K1C rats were considered hypertensive when presenting SBP higher than 160 mmHg and underwent resveratrol (20 mg/kg), captopril (6 or 12 mg/kg), or resveratrol (20 mg/kg) combined with captopril (6 or 12 mg/kg) treatment for 3 weeks. Nine weeks after surgery, rat SBP was measured, and rat thoracic aorta was isolated for histological assays with hematoxylin/eosin or Picrosirius Red to evaluate aortic remodeling and fibrosis, respectively.
  
  
  RESULTS
  Oral treatment of 2K1C hypertensive rats with resveratrol (20 mg/kg) combined with the dose-dependent ACEi captopril (6 and 12 mg/kg) resulted in lesser aortic thickening and reduced aortic fibrosis. Resveratrol (20 mg/kg) promoted a more expressive hypotensive effect with captopril (12 mg/kg) in 2K1C rats than the treatment with isolated captopril (12 mg/kg).
  
  
  CONCLUSIONS
  Resveratrol improves the vasoprotective effects promoted by captopril on aortic remodeling and fibrosis during renovascular hypertension probably by synergic mechanisms involving antioxidant actions and nitric oxide generation.
authors.affiliation: Faculty of Medicine, University of Ribeirão Preto (UNAERP), Medicine School Ribeirão Preto, SP, Brazil.
authors.forename: Henrique Melo
authors.initials: HM
authors.lastname: Natalin
authors.affiliation: Faculty of Medicine, University of Ribeirão Preto (UNAERP), Medicine School Ribeirão Preto, SP, Brazil.
authors.forename: Arthur Feierabend Engracia
authors.initials: AF
authors.lastname: Garcia
authors.affiliation: Department of Cellular and Molecular Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brasil.
authors.forename: Leandra Naira Zambeli
authors.initials: LN
authors.lastname: Ramalho
authors.affiliation: Faculty of Medicine, University of Ribeirão Preto (UNAERP), Medicine School Ribeirão Preto, SP, Brazil. Electronic address: carolbaraldi@hotmail.com.
authors.forename: Carolina Baraldi Araujo
authors.initials: CB
authors.lastname: Restini
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D002216:Captopril / Q000494:pharmacology*; D004357:Drug Synergism; D005355:Fibrosis / Q000473:pathology; D006978:Hypertension, Renovascular / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D013267:Stilbenes; D002216:Captopril; D000077185:Resveratrol
keywords: Captopril; Oxidative stress; Renovascular hypertension; Resveratrol; Vascular fibrosis; Vascular remodeling