Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet. Hypertension 2008 Feb;51(2):352-9
Date
12/26/2007Pubmed ID
18158349Pubmed Central ID
PMC2491336DOI
10.1161/HYPERTENSIONAHA.107.099499Scopus ID
2-s2.0-38549099062 (requires institutional sign-in at Scopus site) 104 CitationsAbstract
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.
Author List
Knight SF, Quigley JE, Yuan J, Roy SS, Elmarakby A, Imig JDMESH terms used to index this publication - Major topics in bold
AlbuminuriaAnimals
Arterioles
Biomarkers
Blood Glucose
Blood Pressure
Body Weight
Chemokine CCL2
Cholesterol
Cytokines
Dietary Fats
Dose-Response Relationship, Drug
Endothelium, Vascular
Gene Expression Profiling
Inflammation
Inflammation Mediators
Insulin Resistance
Kidney
Kidney Cortex
Leptin
Macrophages
Male
RNA, Messenger
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Receptors, CCR1
