Published Online
on December 24, 2007

A more recent version of this article appeared on February 1, 2008

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Submitted on August 7, 2007
Revised on August 24, 2007

Endothelial Dysfunction and the Development of Renal Injury in Spontaneously Hypertensive Rats Fed a High-Fat Diet

Sarah F. Knight^*; Jeffrey E. Quigley; Jianghe Yuan; Siddhartha S. Roy; Ahmed Elmarakby; and John D. Imig

From the Vascular Biology Center, Medical College of Georgia, Augusta.

^* To whom correspondence should be addressed. E-mail: saknight{at}mail.mcg.edu.

Abstract—Obesity and hypertension have been identified as cardiovascular risk factors that contribute to the progression of end-stage renal disease. To examine the mechanisms by which a high-fat diet and hypertension contribute to endothelial dysfunction and renal injury, 8-week–old male spontaneously hypertensive rats and Wistar rats were fed a high-fat (36% fat) or a normal-fat (7% fat) diet for 10 weeks. The high-fat diet increased body weight in Wistar and hypertensive rats by 25 and 31 g, respectively. Systolic blood pressure was higher in the hypertensive rats compared with Wistar rats; however, blood pressure was unaltered by the high-fat diet. Afferent arteriole response to acetylcholine was impaired in the high-fat groups after just 3 weeks. Renal macrophage infiltration was increased in the hypertensive high-fat group compared with others, and monocyte chemoattractant protein-1 excretion was increased in both of the high-fat–fed groups. Renal PCR arrays displayed significant increases in 2 inflammatory genes in hypertensive rats fed a normal diet, 1 gene was increased in high-fat–fed Wistar rats, whereas 12 genes were increased in high-fat–fed hypertensive rats. Urinary albumin excretion was increased in the hypertensive rats compared with the Wistar rats, which was further exacerbated by the high-fat diet. Glomerular nephrin expression was reduced and desmin was increased by the high-fat diet in the hypertensive rats. Our results indicate that endothelial dysfunction precedes renal injury in normotensive and spontaneously hypertensive rats fed a high-fat diet, and hypertension with obesity induces a powerful inflammatory response and disruption of the renal filtration barrier.

Key words: obesity • inflammation • hypertension • renal disease

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