Resveratrol prevents hypertension and cardiac hypertrophy in hypertensive rats and mice

Vernon W. Dolinsky, Subhadeep Chakrabarti, Troy J. Pereira, Tatsujiro Oka, Jody Levasseur, Donna Beker, Beshay N. Zordoky, Jude S. Morton, Jeevan Nagendran, Gary D. Lopaschuk, Sandra T. Davidge, Jason R.B. Dyck

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Resveratrol (RESV) is a polyphenol with pleiotropic effects that include reduction of oxidative stress and increased vascular nitric oxide (NO) production. However, whether or not RESV can prevent rises in blood pressure (BP) is controversial and remains to be firmly established. The purpose of this study was to determine whether RESV attenuates elevated BP and subsequent adaptive cardiac hypertrophy and to better understand the mechanisms involved. The spontaneously hypertensive rat (SHR) and the angiotensin (Ang)-II infused mouse were used as hypertensive models. Compared to a standard control diet, consumption of diets containing RESV by SHRs and Ang-II hypertensive mice, markedly prevented rises in systolic BP. In addition, flow-mediated vasodilation was significantly improved by RESV in SHRs. RESV also reduced serum and cardiac levels of the lipid peroxidation by-product, 4-hydroxy-2-nonenal in the hypertensive rodents and inhibited the production of superoxide in human-derived endothelial cells. Analysis of mesenteric arteries from SHRs and Ang-II infused mice demonstrated that RESV increased endothelial NO synthase (eNOS) phosphorylation by enhancing the LKB1/adenosine monophosphate (AMP)-activated protein kinase (AMPK) signal transduction pathway. Moreover, RESV reduced hypertrophic growth of the myocardium through reduced hemodynamic load and inhibition of the p70 S6 kinase pro-hypertrophic signaling cascade. Overall, we show that high dose RESV reduces oxidative stress, improves vascular function, attenuates high BP and prevents cardiac hypertrophy through the preservation of the LKB1-AMPK-eNOS signaling axis.

Original languageEnglish (US)
Pages (from-to)1723-1733
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1832
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by The Canadian Hypertension Society–Pfizer Award to JRBD, grants from the Canadian Institutes of Health Research (CIHR) to STD, GDL and JRBD, and a grant from the Heart and Stroke Foundation of Canada (HSFC) to VWD. JRBD is an Alberta Heritage Foundation for Medical Research (AHFMR) Senior Scholar. GDL is an AHFMR Scientist. STD is an AHFMR Scientist and Canada Research Chair in Women's Cardiovascular Health.

Keywords

  • Hypertension
  • Left ventricular hypertrophy
  • Lipid peroxide
  • Nitric oxide
  • Resveratrol
  • Signal transduction

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