title: Long-term high salt diet causes hypertension and alters renal cytokine gene expression profiles in Sprague-Dawley rats.
abstract: OBJECTIVE
  The present study examines whether a long-term high salt diet causes hypertension and renal injury in normal subjects [Sprague-Dawley (SD) rats] and alters renal cytokine-related gene expression profiles.
  
  
  METHODS
  Four 10 week old male SD rats received a high salt diet (HS, 8%) and the other 4 SD rats received a normal salt diet (NS, 0.5%) for 8 weeks. Mean arterial pressure (MAP) and renal damages such as albuminuria and histological renal injury were determined. The relative mRNA levels of 514 cytokine-related genes (normalized by beta-actin) in rat kidneys following NS or HS were determined quantitatively through analysis of 4 sets of gene expression profiles using the mouse cDNA membrane microarrays.
  
  
  RESULTS
  We demonstrated that 8 weeks of HS diet increased MAP [(140.0+/-5.3) vs (112.0+/-2.2) mmHg; 1 mmHg=0.133 kPa, P<0.01], albuminuria [(41.4+/-3.2) vs (20.1+/-4.5) mg/d; P<0.01], and caused histological renal injury in SD rats, compared to NS group. Of the 514 genes in the array, there were 27 (5.25%) genes with significantly different expression in the kidney of SD rats with HS compared to those of SD rats with NS. Functional clustering analysis indicated the following functional pathways related to high salt diet-induced hypertension: (1) pro-inflammatory response ( upward arrowIL-17, CCL28; downward arrow NFkappabib); (2) endothelial dysfunction ( downward arrowVEGF-A, VEGF-B, endoglin); (3) pro-matrix formation ( upward arrowosteopontin, IGFBP-5; downward arrow IFN-gamma); and (4) attenuated cell survival and differentiation ( downward arrowCNTF, IGF-II R, ephrin-B1). Northern blot confirmed that 8 weeks of HS diet significantly decreased renal expression of VEGF mRNA, compared to NS group (P<0.01). ELISA showed that HS diet significantly decreased renal protein levels of VEGF and CCL28.
  
  
  CONCLUSIONS
  These findings support the hypothesis that hypertension can be induced in normal rats by a long-term high salt diet, which is associated with increased renal injury and marked changes in renal cytokine gene expression profiles that are closely related to the pro-inflammatory response, pro-matrix formation, endothelial dysfunction, and attenuated cell survival and differentiation.
authors.affiliation: Department of Physiology & Biophysics, University of Mississippi Medical Center Jackson, Mississippi 39216, USA. jgu@physiology.umsmed.edu
authors.forename: Jian-wei
authors.initials: JW
authors.lastname: Gu
authors.forename: Emily
authors.initials: E
authors.lastname: Young
authors.forename: Zhi-jun
authors.initials: ZJ
authors.lastname: Pan
authors.forename: Kevan B
authors.initials: KB
authors.lastname: Tucker
authors.forename: Megan
authors.initials: M
authors.lastname: Shparago
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Amelia Purser
authors.initials: AP
authors.lastname: Bailey
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000378:metabolism; D000818:Animals; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006973:Hypertension / Q000209:etiology*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C545986:CCL28 protein, rat; D019742:Chemokines, CC; D016207:Cytokines; D012333:RNA, Messenger; D012982:Sodium, Dietary; D042461:Vascular Endothelial Growth Factor A