Whole grape intake impacts cardiac peroxisome proliferator-activated receptor and nuclear factor kappaB activity and cytokine expression in rats with diastolic dysfunction

Hypertension. 2010 May;55(5):1179-85. doi: 10.1161/HYPERTENSIONAHA.109.149393. Epub 2010 Mar 15.


Prolonged hypertension is the leading cause of heart failure. Failing hearts show reduced peroxisome proliferator-activating receptor (PPAR) activity and enhanced nuclear factor kappaB (NF-kappaB) activity, which together modify cardiac inflammation and fibrosis. In vitro studies suggest that phytochemicals alter PPAR and NF-kappaB activity, but the capabilities of a phytochemical-rich diet are less understood. Grapes contain an array of commonly consumed dietary phytochemicals. In Dahl salt-sensitive hypertensive rats, we showed previously that dietary provision of whole table grape powder (3% weight:weight) for 18 weeks reduced blood pressure, cardiac hypertrophy, and diastolic dysfunction. The hypothesis tested here is that, in this model, phytochemical provision from whole grape powder impacts cardiac PPAR and NF-kappaB activity and their related gene transcripts. Grape-fed rats had enhanced PPAR-alpha and PPAR-gamma DNA binding activity but reduced NF-kappaB DNA binding activity. RT-PCR revealed that grape-fed rats showed upregulated mRNA for PPAR-alpha, PPAR-gamma coactivator-1alpha, PPAR-gamma, and the cytosolic NF-kappaB inhibitor, inhibitor-kappaBalpha. By contrast, grape-fed rats showed downregulated mRNA for tumor necrosis factor-alpha and transforming growth factor-beta1. Finally, grape-fed rats showed significantly reduced cardiac tumor necrosis factor-alpha and transforming growth factor-beta protein expression, increased inhibitor-kappaBalpha expression, and reduced cardiac fibrosis. In the Dahl salt-sensitive rat, chronic intake of grapes altered cardiac transcripts related to PPAR and NF-kappaB that may be significant to the observed diet-associated cardioprotection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / therapeutic use*
  • Cytokines / genetics*
  • Diastole / drug effects
  • Diastole / physiology*
  • Heart Failure, Diastolic / prevention & control
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • PPAR alpha / genetics
  • PPAR gamma / genetics
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / physiology*
  • RNA, Messenger / genetics
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Vitis*


  • Cardiotonic Agents
  • Cytokines
  • NF-kappa B
  • PPAR alpha
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptors
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha