Obesity is the major contributor to vascular dysfunction and inflammation in high-fat diet hypertensive rats

Ahmed A. Elmarakby, John D. Imig

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Obesity and hypertension are the two major risk factors that contribute to the progression of end-stage renal disease. To examine whether hypertension further exacerbates oxidative stress and vascular dysfunction and inflammation in obese rats, four groups of male Sprague - Dawley rats were fed either a normal (7% fat) or high-fat (36% fat) diet for 6 weeks and osmotic pumps were implanted to deliver ANG (angiotensin II) or vehicle for an additional 4 weeks. Treatment with the high-fat diet did not alter ANG-induced hypertension compared with the normal diet (174 ± 6 compared with 170 ± 5 mmHg respectively). Treatment with the high-fat diet increased body weight gain and plasma leptin levels and induced insulin resistance in normotensive and ANG-induced hypertensive rats. Plasma TBARS (thiobarbituric acid-reacting substances), a measure of oxidative stress, were elevated in high-fat diet-fed rats compared with controls (11.2±1 compared with 8.4±1 nmol/ml respectively) and was increased further in ANG-induced hypertensive rats fed a high-fat diet (18.8±2.2 nmol/ml). Urinary nitrite excretion was also decreased in rats fed a high-fat diet without or with ANG infusion compared with controls. Afferent arteriolar relaxation to acetylcholine was impaired in rats fed the high-fat diet without or with ANG infusion. Renal cortical TNF-α (tumour necrosis factor-α), COX-2 (cyclo-oxygenase-2) and phospho-IKK (inhibitor of nuclear factor κB kinase) expression increased in high-fat diet-fed rats compared with normal diet-fed rats. The increases in phospho-IKK and COX-2 expression were elevated further in ANG-induced hypertensive rats fed the high-fat diet. These results suggest that ANG-induced hypertension exacerbates oxidative stress and renal inflammation without further impairment in vascular dysfunction in high-fat diet-induced obesity.

Original languageEnglish (US)
Pages (from-to)291-301
Number of pages11
JournalClinical Science
Volume118
Issue number4
DOIs
StatePublished - Jan 1 2010

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Keywords

  • Angiotensin II
  • High-fat diet
  • Hypertension
  • Inflammation
  • Obesity
  • Oxidative stress
  • Vascular dysfunction

ASJC Scopus subject areas

  • Medicine(all)

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