Insulin Resistance Impairs Endothelial Function but not Adrenergic Reactivity or Vascular Structure in Fructose‐fed Rats

Romanko, Olga P.; Ali, Mohammed Farid; Mintz, James D.; Stepp, David W.

doi:10.1080/10739680902832795

Cited by 18 publications

(17 citation statements)

References 41 publications

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“…These data are consistent with our recent findings where 10 weeks of high fat diet treatment also increased plasma insulin levels in WKY and SHR [8]. Insulin resistance has been shown to contribute to the development of endothelial dysfunction [24, 40] as high insulin levels induce renal hemodynamic changes, glomerular hypertrophy, and mesangial cell proliferation [41, 42]. Together, these data suggest that high fat diet induced insulin resistance and ANG hypertension did not potentiate this effect.…”

Section: Discussionsupporting

confidence: 93%

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

Elmarakby

Imig

2009

Clinical Science

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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 normal (7% fat) or high fat (36% fat) diet for 6 weeks and osmotic pumps were implanted to deliver angiotensin II (ANG) or vehicle for four additional weeks. High fat diet treatment did not alter ANG-induced hypertension compared to normal diet (174±6 vs. 170±5 mmHg, respectively). High fat diet treatment increased body weight gain and plasma leptin levels and induced insulin resistance in normotensive and ANG hypertensive rats. Plasma TBARs, a measure of oxidative stress, was elevated in high fat diet fed rats compared to control (11.2±1 vs. 8.4±1 nmol/ml, respectively) and was further increased in ANG hypertensive rats fed high fat diet (18.8±2.2 nmol/ml). Urinary nitrite excretion was also decreased in rats fed high fat diet with or without ANG infusion compared to control. Afferent arteriolar relaxation to acetylcholine was impaired in high fat fed rats with or without ANG infusion. Renal cortical TNF-α, COX-2, and phospho-IKK expression increased in high fat diet compared to normal diet fed rats. The increases in phospho-IKK and COX-2 expression were further elevated in ANG hypertensive rats fed high fat diet. These data 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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Section: Discussionsupporting

confidence: 93%

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

Elmarakby

Imig

2009

Clinical Science

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“…; Romanko et al. ) suggesting that findings in that model may reflect the artificial processes involved in its generation rather than metabolic dysfunction as manifest by normal disease processes. While it is likely simplistic to assume the hypertension is the sole drive of vascular dysfunction in obesity, this study adds to a growing body of evidence that it may be the primary one.…”

Section: Discussionmentioning

confidence: 99%

Vascular effects of deletion of melanocortin-4 receptors in rats

et al. 2013

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Obesity is a major cause of hypertension, but links between the obese and hypertensive states remain incompletely understood. A major component of cardiovascular function in obese individuals is a state of sympathoactivation. A postulated mechanism of this sympathoactivation is the activation of specific classes of neurons commonly associated with metabolic control, which also affect sympathetic outflow to cardiovascular targets. One class of neurons is characterized by expression of melanocortin-4 receptors (MC4R) which are activated by metabolic signals such as leptin and insulin. In this study, we examined the effects of deletion of MC4R in a novel rat model. MC4R knockout (KO) rats are obese and profoundly insulin resistant without frank diabetes. Despite these conditions, MC4R KO rats are normotensive. Moderate bradycardia and significant increases in peripheral resistance were evident in MC4R KO rats. To determine if the dissociation between hypertension and obesity was associated with changes in vascular function, in vitro reactivity to vasoactive agents and in vivo reactivity to sympathetic blockade were examined. Vasodilator function was not affected by obesity in MC4R KO rats. Reactivity to phenylephrine was reduced, suggesting desensitization of adrenergic signaling. In response to ganglionic blockade with mecamylamine, blood pressure and hindlimb resistance fell more in MC4R KO rats, suggesting that sympathoactivation of the vascular was still evident, despite the absence of hypertension. These findings suggest that obesity causes sympathoactivation of the vasculature despite the absence of MC4R. Dissociation of obesity from hypertension in this model may reflect more renal mechanisms of blood pressure control.

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“…It has been shown that FRD promotes decreases in endothelial NO production [9] and vasorelaxation [10,11] as well as impaired insulin-induced vasodilation [9]. Further, the FRD model is also useful to test the effects of different preventive strategies aimed at decreasing MS vascular morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue

Rebolledo

Marra

et al. 2010

Cardiovasc Diabetol

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AimTo test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility.MethodsAdult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K+-induced depolarization using intact and thereafter PVAT-deprived rings.ResultsComparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats.ConclusionsFRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.

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Insulin Resistance Impairs Endothelial Function but not Adrenergic Reactivity or Vascular Structure in Fructose‐fed Rats

Cited by 18 publications

References 41 publications

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

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

Vascular effects of deletion of melanocortin-4 receptors in rats

Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue

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