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

Elmarakby, Ahmed A.; Imig, John D.

doi:10.1042/cs20090395

Cited by 77 publications

(60 citation statements)

References 54 publications

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“…2). Similarly, inflammatory markers and oxidative stress markers were significantly increased in the renal cortex of Sprague-Dawley rats treated for 6 wk with a high-fat diet (58% fat-derived calories and a total of 5.4 kcal/g, compared with normal chow with 12% fat-derived calories and a total of 3.3 kcal/g) (44). Infusion of angiotensin II by osmotic pumps and high-fat feeding for another 4 wk potentiated oxidative stress and renal inflammation, without further exacerbating vascular dysfunction.…”

Section: A High-fat Diet As a Risk Factor For Ckdmentioning

confidence: 96%

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

Odermatt

2011

American Journal of Physiology-Renal Physiology

218

128

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The Western-style diet is characterized by its highly processed and refined foods and high contents of sugars, salt, and fat and protein from red meat. It has been recognized as the major contributor to metabolic disturbances and the development of obesity-related diseases including type 2 diabetes, hypertension, and cardiovascular disease. Also, the Western-style diet has been associated with an increased incidence of chronic kidney disease (CKD). A combination of dietary factors contributes to the impairment of renal vascularization, steatosis and inflammation, hypertension, and impaired renal hormonal regulation. This review addresses recent progress in the understanding of the association of the Western-style diet with the induction of dyslipidemia, oxidative stress, inflammation, and disturbances of corticosteroid regulation in the development of CKD. Future research needs to distinguish between acute and chronic effects of diets with high contents of sugars, salt, and fat and protein from red meat, and to uncover the contribution of each component. Improved therapeutic interventions should consider potentially altered drug metabolism and pharmacokinetics and be combined with lifestyle changes. A clinical assessment of the long-term risks of whole-body disturbances is strongly recommended to reduce metabolic complications and cardiovascular risk in kidney donors and patients with CKD.

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Section: A High-fat Diet As a Risk Factor For Ckdmentioning

confidence: 96%

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

Odermatt

2011

American Journal of Physiology-Renal Physiology

218

128

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“…Endothelial dysfunction, due to altered NO release and metabolism, has been reported as participating in these vascular alterations (Javeshghani et al, 2009;Belin de Chantemèle et al, 2010;Miâdi-Messaoud et al, 2010). The angiotensin II system also seems to be involved in obesityassociated alterations in both humans and rats (de las Heras et al, 2009;Elmarakby and Imig, 2010;Katragadda and Arora, 2010;Rueda-Clausen et al, 2010). The sympathetic nervous system seems to participate in the pathological cardiovascular and metabolic alterations associated with obesity (Prior et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Drugs targeting the cardiovascular system such as adrenoceptor antagonists, angiotensin converting enzyme inhibitors (ACEI) and angiotensin AT1 receptor antagonists (ARBs) have shown beneficial effects in metabolic and cardiovascular disorders associated with obesity through several mechanisms involving endothelial factors, inflammation and oxidative stress (de las Heras et al, 2009;Elmarakby and Imig, 2010;Katragadda and Arora, 2010). Statins have also shown anti-inflammatory effects, as well as improvement in NO availability through hypolipidemic and pleiotropic mechanisms (Tan et al, 2002;Gelosa et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Blanco-Rivero

Heras

Martín-Fernández

et al. 2010

British J Pharmacology

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BACKGROUND AND PURPOSEWe investigated whether high-fat diet (HFD)-induced obesity was associated with changed function of components of the mesenteric innervation (adrenergic, sensory and nitrergic), the mechanisms involved and the possible effects of rosuvastatin on these changes. EXPERIMENTAL APPROACHMale Wistar rats were divided into three groups. (i) rats fed a standard diet (control group); (ii) rats fed a HFD (33.5% fat) for 7 weeks; and (iii) rats fed a HFD and treated with rosuvastatin (15 mg·kg) for 7 weeks. Segments of isolated mesenteric arteries were exposed to electric field stimulation (EFS) with or without tetrodotoxin, phentolamine, 7-nitroindazole (7NI) or N w nitro-L-arginine methyl ester (L-NAME). Noradrenaline, ATP and NO release, and nNOS expression were also measured. KEY RESULTSEFS induced a greater frequency-dependent contraction in obese than in control rats. In HFD rats, phentolamine reduced contractions elicited by EFS, but noradrenaline release was greater and ATP release decreased. L-NAME and 7NI increased contractions to EFS in segments from control rats, but not in those from HFD rats. NO release and nNOS expression were lower in arterial segments from HFD rats than in control rats. All these changes in HFD rats were reversed by treatment with rosuvastatin. CONCLUSIONS AND IMPLICATIONSNeural control of mesenteric vasomotor tone was altered in HFD rats. Enhanced adrenergic and diminished nitrergic components both contributed to increased vasoconstrictor responses to EFS. All these changes were reversed by rosuvastatin, indicating novel mechanisms of statins in neural regulation of vascular tone.

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“…large-conductance Ca 2ϩ -activated K ϩ channel; nitric oxide IMPAIRED VASCULAR RESPONSES to vasodilator stimuli, including significantly impaired endothelium-dependent dilation, are frequently observed in both obese individuals (3,5) and animal models of obesity (15,18). Increased sensitivity of vessels to vasoconstrictor stimuli and/or decreased responses to vasodilators may contribute to obesity-induced hypertension and other vascular disease states (4,24).…”

mentioning

confidence: 99%

Dietary obesity increases NO and inhibits BK_Ca-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae

Howitt

Grayson

Morris

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Howitt L, Grayson TH, Morris MJ, Sandow SL, Murphy TV. Dietary obesity increases NO and inhibits BK Ca-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae. Am J Physiol Heart Circ Physiol 302: H2464 -H2476, 2012. First published April 6, 2012 doi:10.1152/ajpheart.00965.2011.-Obesity is a risk factor for hypertension and other vascular disease. The aim of this study was to examine the effect of diet-induced obesity on endothelium-dependent dilation of rat cremaster muscle arterioles. Male Sprague-Dawley rats (213 Ϯ 1 g) were fed a cafeteria-style high-fat or control diet for 16 -20 wk. Control rats weighed 558 Ϯ 7 g compared with obese rats 762 Ϯ 12 g (n ϭ 52-56; P Ͻ 0.05). Diet-induced obesity had no effect on acetylcholine (ACh)-induced dilation of isolated, pressurized (70 mmHg) arterioles, but sodium nitroprusside (SNP)-induced vasodilation was enhanced. ACh-induced dilation of arterioles from control rats was abolished by a combination of the KCa blockers apamin, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), and iberiotoxin (IBTX; all 0.1 mol/l), with no apparent role for nitric oxide (NO). In arterioles from obese rats, however, IBTX had no effect on responses to ACh while the NO synthase (NOS)/guanylate cyclase inhibitors N -nitro-L-arginine methyl ester (L-NAME; 100 mol/l)/1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 mol/l) partially inhibited ACh-induced dilation. Furthermore, NOS activity (but not endothelial NOS expression) was increased in arteries from obese rats. L-NAME/ODQ alone or removal of the endothelium constricted arterioles from obese but not control rats. Expression of caveolin-1 and -2 oligomers (but not monomers or caveolin-3) was increased in arterioles from obese rats. The number of caveolae was reduced in the endothelium of arteries, and caveolae density was increased at the ends of smooth muscle cells from obese rats. Dietinduced obesity abolished the contribution of large-conductance Ca 2ϩ -activated K ϩ channel to ACh-mediated endothelium-dependent dilation of rat cremaster muscle arterioles, while increasing NOS activity and inducing an NO-dependent component. (72). Many of these enzymes and channels are localized within caveolae, as cholesterol-rich invaginations of the plasma membrane (10). Caveolins, the structural proteins of caveolae, have an established role in modulating vascular signaling mechanisms including NO synthase (NOS) and BK Ca activity (1,13,20).Studies on the impact of obesity on endothelium-dependent vasodilation have focused on impaired NO-mediated responses and, in particular, the altered endothelial NOS (eNOS) activity and NO bioavailability associated with inflammatory mediators and oxidative stress (24, 53). Decreased NO-dependent vasodilation, as an apparent consequence of oxidative stress, has been observed in animal models of obesity (16,18,25,26). In smaller arteries and arterioles, however, particularly those in skeletal muscle (43), NO generally makes a relatively minor...

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

Cited by 77 publications

References 54 publications

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Dietary obesity increases NO and inhibits BK_Ca-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae

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

Cited by 77 publications

References 54 publications

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Dietary obesity increases NO and inhibits BKCa-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae

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Dietary obesity increases NO and inhibits BK_Ca-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae