Obesity is the major contributor to vascular  dysfunction and inflammation in high-fat diet  hypertensive rats.
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.
Elmarakby
Ahmed A
AA
Department of Oral Biology/Pharmacology, Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, U.S.A.. aelmarakby@mcg.edu
Imig
John D
JD
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009393:Nephritis / Q000209:etiology; D009573:Nitrites / Q000652:urine; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014662:Vasoconstrictor Agents; D015430:Weight Gain
D001786:Blood Glucose; D004041:Dietary Fats; D008055:Lipids; D016328:NF-kappa B; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D000109:Acetylcholine