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
Date
09/05/2009Pubmed ID
19728860Pubmed Central ID
PMC2842481DOI
10.1042/CS20090395Scopus ID
2-s2.0-70549099724 (requires institutional sign-in at Scopus site) 77 CitationsAbstract
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.
Author List
Elmarakby AA, Imig JDMESH terms used to index this publication - Major topics in bold
AcetylcholineAngiotensin II
Animals
Blood Glucose
Blood Pressure
Cyclooxygenase 2
Dietary Fats
Endothelium, Vascular
Hypertension
I-kappa B Kinase
Insulin Resistance
Kidney
Lipids
Male
NF-kappa B
Nephritis
Nitrites
Obesity
Oxidative Stress
Rats
Rats, Sprague-Dawley
Thiobarbituric Acid Reactive Substances
Tumor Necrosis Factor-alpha
Vasoconstrictor Agents
Weight Gain
