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Activation of Renal (Pro)Renin Receptor Contributes to High Fructose-Induced Salt Sensitivity.

Publication ,  Journal Article
Xu, C; Lu, A; Lu, X; Zhang, L; Fang, H; Zhou, L; Yang, T
Published in: Hypertension
February 2017

A high-fructose diet is shown to induce salt-sensitive hypertension, but the underlying mechanism largely remains unknown. The major goal of the present study was to test the role of renal (pro)renin receptor (PRR) in this model. In Sprague-Dawley rats, high-fructose intake increased renal expression of full-length PRR, which were attenuated by allopurinol. High-fructose intake also upregulated renal mRNA and protein expression of sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter, as well as in vivo Na/K/2Cl cotransporter activity, all of which were nearly completely blocked by a PRR decoy inhibitor PRO20 or allopurinol treatment. Parallel changes were observed for indices of intrarenal renin-angiotensin-system including renal and urinary renin and angiotensin II levels. Radiotelemetry demonstrated that high-fructose or a high-salt diet alone did not affect mean arterial pressure, but the combination of the 2 maneuvers induced a ≈10-mm Hg increase of mean arterial pressure, which was blunted by PRO20 or allopurinol treatment. In cultured human kidney 2 cells, both fructose and uric acid increased protein expression of soluble PRR in a time- and dose-dependent manner; fructose-induced PRR upregulation was inhibited by allopurinol. Taken together, our data suggest that fructose via uric acid stimulates renal expression of PRR/soluble PRR that stimulate sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter expression and intrarenal renin-angiotensin system to induce salt-sensitive hypertension.

Duke Scholars

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Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

February 2017

Volume

69

Issue

2

Start / End Page

339 / 348

Location

United States

Related Subject Headings

  • Renin-Angiotensin System
  • Receptors, Cell Surface
  • Rats, Sprague-Dawley
  • Rats
  • Prorenin Receptor
  • Male
  • Kidney
  • Hypertension
  • Humans
  • Fructose
 

Citation

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Xu, C., Lu, A., Lu, X., Zhang, L., Fang, H., Zhou, L., & Yang, T. (2017). Activation of Renal (Pro)Renin Receptor Contributes to High Fructose-Induced Salt Sensitivity. Hypertension, 69(2), 339–348. https://doi.org/10.1161/HYPERTENSIONAHA.116.08240

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

February 2017

Volume

69

Issue

2

Start / End Page

339 / 348

Location

United States

Related Subject Headings

  • Renin-Angiotensin System
  • Receptors, Cell Surface
  • Rats, Sprague-Dawley
  • Rats
  • Prorenin Receptor
  • Male
  • Kidney
  • Hypertension
  • Humans
  • Fructose