title: Activation of Renal (Pro)Renin Receptor Contributes to High Fructose-Induced Salt Sensitivity.
abstract: 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.
authors.affiliation: From the Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China (C.X., A.L., X.L., L.Z., H.F., L.Z., T.Y.); Internal Medicine, University of Utah, Salt Lake City (C.X., X.L., T.Y.); and Veterans Affairs Medical Center, Salt Lake City, Utah (X.L., T.Y.).
authors.forename: Chuanming
authors.initials: C
authors.lastname: Xu
authors.affiliation: From the Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China (C.X., A.L., X.L., L.Z., H.F., L.Z., T.Y.); Internal Medicine, University of Utah, Salt Lake City (C.X., X.L., T.Y.); and Veterans Affairs Medical Center, Salt Lake City, Utah (X.L., T.Y.).
authors.forename: Aihua
authors.initials: A
authors.lastname: Lu
authors.affiliation: From the Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China (C.X., A.L., X.L., L.Z., H.F., L.Z., T.Y.); Internal Medicine, University of Utah, Salt Lake City (C.X., X.L., T.Y.); and Veterans Affairs Medical Center, Salt Lake City, Utah (X.L., T.Y.).
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Lu
authors.affiliation: From the Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China (C.X., A.L., X.L., L.Z., H.F., L.Z., T.Y.); Internal Medicine, University of Utah, Salt Lake City (C.X., X.L., T.Y.); and Veterans Affairs Medical Center, Salt Lake City, Utah (X.L., T.Y.).
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China (C.X., A.L., X.L., L.Z., H.F., L.Z., T.Y.); Internal Medicine, University of Utah, Salt Lake City (C.X., X.L., T.Y.); and Veterans Affairs Medical Center, Salt Lake City, Utah (X.L., T.Y.).
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: From the Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China (C.X., A.L., X.L., L.Z., H.F., L.Z., T.Y.); Internal Medicine, University of Utah, Salt Lake City (C.X., X.L., T.Y.); and Veterans Affairs Medical Center, Salt Lake City, Utah (X.L., T.Y.).
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: From the Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China (C.X., A.L., X.L., L.Z., H.F., L.Z., T.Y.); Internal Medicine, University of Utah, Salt Lake City (C.X., X.L., T.Y.); and Veterans Affairs Medical Center, Salt Lake City, Utah (X.L., T.Y.). Tianxin.Yang@hsc.utah.edu.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005632:Fructose / Q000009:adverse effects / Q000633:toxicity; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D005632:Fructose; D000493:Allopurinol; D000093342:Prorenin Receptor
keywords: fructose diet; hypertension; renin–angiotensin system; uric acid