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

Clin Sci (Lond). 2010 Feb;118(4):291-301. doi: 10.1042/CS20090395.


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 +/- 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-alpha(tumour necrosis factor-alpha), COX-2(cyclo-oxygenase-2) and phospho-IKK (inhibitor of nuclear factor k B 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Angiotensin II
  • Animals
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Cyclooxygenase 2 / metabolism
  • Dietary Fats / administration & dosage
  • Dietary Fats / adverse effects*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Hypertension / chemically induced
  • Hypertension / complications*
  • Hypertension / metabolism
  • I-kappa B Kinase / metabolism
  • Insulin Resistance / physiology
  • Kidney / metabolism
  • Lipids / blood
  • Male
  • NF-kappa B / metabolism
  • Nephritis / etiology
  • Nitrites / urine
  • Obesity / complications*
  • Obesity / metabolism
  • Oxidative Stress*
  • Rats
  • Rats, Sprague-Dawley
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasoconstrictor Agents
  • Weight Gain


  • Blood Glucose
  • Dietary Fats
  • Lipids
  • NF-kappa B
  • Nitrites
  • Thiobarbituric Acid Reactive Substances
  • Tumor Necrosis Factor-alpha
  • Vasoconstrictor Agents
  • Angiotensin II
  • Cyclooxygenase 2
  • I-kappa B Kinase
  • Acetylcholine