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.
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Research Article|
November 16 2009
Obesity is the major contributor to vascular dysfunction and inflammation in high-fat diet hypertensive rats
Ahmed A. Elmarakby;
*Department of Oral Biology/Pharmacology, Medical College of Georgia, Augusta, GA 30912, U.S.A.
†Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, U.S.A.
Correspondence: Dr Ahmed A. Elmarakby (email [email protected]).
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John D. Imig
John D. Imig
‡Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, U.S.A.
§Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, U.S.A.
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Publisher: Portland Press Ltd
Received:
July 23 2009
Revision Received:
August 27 2009
Accepted:
September 03 2009
Accepted Manuscript online:
September 03 2009
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 118 (4): 291–301.
Article history
Received:
July 23 2009
Revision Received:
August 27 2009
Accepted:
September 03 2009
Accepted Manuscript online:
September 03 2009
Citation
Ahmed A. Elmarakby, John D. Imig; Obesity is the major contributor to vascular dysfunction and inflammation in high-fat diet hypertensive rats. Clin Sci (Lond) 1 February 2010; 118 (4): 291–301. doi: https://doi.org/10.1042/CS20090395
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