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THE DIETARY FLAVONOID QUERCETIN MODULATES ENDOTHELIAL NITRIC OXIDE:SUPEROXIDE IMBALANCE VIA EXPRESSION CHANGES IN P47PHOX UNDER HYPERTENSIVE CONDITIONS IN VITRO
  1. HS Jones1,2,
  2. A Gordon1,2,
  3. SG Magwenzi2,
  4. K Naseem2,
  5. SL Atkin1,3,
  6. FL Courts1,2,4
  1. 1HONEI, Hull-York Medical School, University of Hull, Hull, UK
  2. 2Centre for Cardiovascular and Metabolic Research, Hull-York Medical School, University of Hull, Hull, UK
  3. 3Weill Cornell Medical College Qatar, Doha, Qatar
  4. 4Institute of Food Research, Norwich Research Park, Norwich, UK

Abstract

Quercetin reduces blood pressure in hypertensive, but not normotensive individuals. Ex vivo tissue has implicated NADPH oxidase signalling and ROS formation in the mechanism of action in vascular smooth muscle, however there has been no assessment of the role of the endothelium in the anti-hypertensive effects of quercetin. This study describes an endothelial cell model of hypertension and its use to probe the anti-hypertensive effects of quercetin.

Angiotensin II (100 nM, 8 h) rendered Human Umbilical Vein Endothelial Cells (HUVEC) hypertensive, characterised by decreased nitric oxide availability (15±4%, p<0.05) and increased superoxide production (136±5%, p<0.001, measured by LC-MS detection of dihydroethidium reaction products) compared to controls. Co-exposure of HUVEC to angiotensin II and quercetin (3 µM, 8 h) restored the nitric oxide:superoxide imbalance to control (normotensive) levels without altering eNOS mRNA expression. Quercetin alone had no effects upon nitric oxide, superoxide or eNOS mRNA levels. The NADPH oxidase subunit p47phox was increased at the protein level in hypertensive cells (30±14% of control, p<0.05), which was prevented by quercetin co-treatment. These changes were reflected at the mRNA level. Protein kinase C (PKC) activity (western blotting) increased after angiotensin II treatment (262±60%, p<0.05), which was not prevented by co-treatment with quercetin (3 µM, 8 h).

In summary, quercetin restores nitric oxide:superoxide imbalance in hypertensive endothelial cells to control levels, in a PKC-independent manner, with down-regulation of p47phox also observed. No effects of quercetin upon control cells are reported.

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