Long-term high-salt diet causes hypertension and decreases renal expression of vascular endothelial growth factor in Sprague-Dawley rats

We seek to determine: 1) whether a long-term high-salt (HS) diet induces hypertension and renal injury in Sprague-Dawley (SD) rats and 2) whether the HS diet-induced hypertension and renal injury are associated with decreased renal vascular endothelial growth factor (VEGF) expression. Twelve 10-week-old male SD rats received a HS diet (8%) and 12 SD rats received a normal salt diet (NS, 0.5%) for 8 weeks. Using a tail cuff, weekly monitoring showed that blood pressure (BP) increased significantly after 6, 7, and 8 weeks in the HS group, compared with the NS group (P < .01). At 4 weeks and 8 weeks of diet, mean arterial pressure (MAP) was determined in conscious rats by continuous monitoring through a catheter placed in the carotid artery. MAP was not significantly different between HS and NS group in 4 weeks, but was significantly higher in HS than NS group (140 +/- 5.3 vs. 112 +/- 2.2 mm Hg; P < .01) in 8 weeks. Increased proteinuria and albuminuria were associated with marked renal histologic abnormalities in the HS group, compared with those in the NS group. Northern blot and enzyme-linked immunosorbent assay (ELISA) demonstrated that 8 weeks of HS diet significantly decreased renal expression of VEGF mRNA and protein, compared with the NS group (P < .01). In 8 weeks, total urinary excretion of sFlt-1 was significantly higher in HS than NS group (9.28 +/- 1.05 vs. 2.05 +/- 0.55 ng/day; P < .01), whereas the plasma levels of sFlt-1 remained stable. These results suggest that a long-term HS diet induces renal injury and hypertension, which are associated with decreased renal VEGF expression in normotensive rodent animals. J Am Soc Hypertens 2008;2(4): 275-285. (C) 2008 American Society of Hypertension. All rights reserved.