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 Abdelrazik Elmarakby, John D. Imig

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)352-359
Number of pages8
JournalHypertension
Volume51
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint

High Fat Diet
Inbred SHR Rats
Fats
Kidney
Wounds and Injuries
Wistar Rats
Blood Pressure
Hypertension
Obesity
Genes
Diet
Desmin
Chemokine CCL2
Arterioles
Acetylcholine
Chronic Kidney Failure
Albumins
Macrophages
Body Weight
Polymerase Chain Reaction

Keywords

  • Hypertension
  • Inflammation
  • Obesity
  • Renal disease

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet. / Knight, Sarah F.; Quigley, Jeffrey E.; Yuan, Jianghe; Roy, Siddhartha S.; Elmarakby, Ahmed Abdelrazik; Imig, John D.

In: Hypertension, Vol. 51, No. 2, 01.02.2008, p. 352-359.

Research output: Contribution to journalArticle

Knight, Sarah F. ; Quigley, Jeffrey E. ; Yuan, Jianghe ; Roy, Siddhartha S. ; Elmarakby, Ahmed Abdelrazik ; Imig, John D. / Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet. In: Hypertension. 2008 ; Vol. 51, No. 2. pp. 352-359.
@article{dca966a495ff40d1a4a6d2a6dbd7f890,
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.",
keywords = "Hypertension, Inflammation, Obesity, Renal disease",
author = "Knight, {Sarah F.} and Quigley, {Jeffrey E.} and Jianghe Yuan and Roy, {Siddhartha S.} and Elmarakby, {Ahmed Abdelrazik} and Imig, {John D.}",
year = "2008",
month = "2",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.107.099499",
language = "English (US)",
volume = "51",
pages = "352--359",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet

AU - Knight, Sarah F.

AU - Quigley, Jeffrey E.

AU - Yuan, Jianghe

AU - Roy, Siddhartha S.

AU - Elmarakby, Ahmed Abdelrazik

AU - Imig, John D.

PY - 2008/2/1

Y1 - 2008/2/1

N2 - 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.

AB - 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.

KW - Hypertension

KW - Inflammation

KW - Obesity

KW - Renal disease

UR - http://www.scopus.com/inward/record.url?scp=38549099062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38549099062&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.107.099499

DO - 10.1161/HYPERTENSIONAHA.107.099499

M3 - Article

C2 - 18158349

AN - SCOPUS:38549099062

VL - 51

SP - 352

EP - 359

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 2

ER -