title: Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet.
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.
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA. saknight@mail.mcg.edu
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Knight
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Quigley
authors.forename: Jianghe
authors.initials: J
authors.lastname: Yuan
authors.forename: Siddhartha S
authors.initials: SS
authors.lastname: Roy
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elmarakby
authors.forename: John D
authors.initials: JD
authors.lastname: Imig
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000097:blood; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D007672:Kidney Cortex / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008264:Macrophages / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D054389:Receptors, CCR1 / Q000235:genetics
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C491766:Ccl2 protein, rat; C515302:Ccr1 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D004041:Dietary Fats; D018836:Inflammation Mediators; D020738:Leptin; D012333:RNA, Messenger; D054389:Receptors, CCR1; D002784:Cholesterol