Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.

Steinberg, Helmut O.; Tarshoby, Manal; Monestel, Robert; Hook, Ginger; Cronin, Jessica; Johnson, Ann; Bayazeed, Basel; Baron, Alain

doi:10.1172/jci119636

Cited by 701 publications

(487 citation statements)

References 15 publications

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“…This antihypertensive effect has been related to the beneficial properties of resveratrol on endothelial dysfunction. In the model of obese Zucker rats, as well as in subjects with insulin resistance, FFA are involved both in insulin resistance and in the inhibition of aortic eNOS activity through an oxidative mechanism [50,51]. The present results show that the chronic daily administration of resveratrol restores aortic expression of eNOS in obese Zucker rats, an effect which could explain the antihypertensive effects of this polyphenol in the insulin resistance model described, and which would be mediated by its antioxidant properties [15].…”

Section: Discussionsupporting

confidence: 53%

Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats

Rivera

Morón

Zarzuelo

et al. 2009

Biochemical Pharmacology

353

251

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Section: Discussionsupporting

confidence: 53%

Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats

Rivera

Morón

Zarzuelo

et al. 2009

Biochemical Pharmacology

353

251

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“…In this regard, it is interesting to note that a chronic improvement in metabolic control did not modify the response to ACh, but restored the ability of insulin to potentiate the vascular response to ACh [35]. Alternatively, insulin might favour EDV by lowering plasma concentrations of NEFA, a substrate that negatively affects EDV [36]. Interestingly, in this context, the largest OGTT-induced NEFA gradient was observed in IGT participants: 76% vs 68% in NGT and 62% in diabetic participants (p<0.01 by Kruskal-Wallis; Table 1).…”

Section: Discussionmentioning

confidence: 98%

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

et al. 2008

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Aims/hypothesis Hyperglycaemia and hyperinsulinaemia have opposite effects on endothelium-dependent vasodilatation in microcirculation, but the net effect elicited by glucose ingestion and the separate influence of glucose tolerance are unknown. Methods In participants with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or diabetic glucose tolerance, multiple plasma markers of both oxidative stress and endothelial activation, and forearm vascular responses (plethysmography) to intra-arterial acetylcholine (ACh) and sodium nitroprusside (SNP) infusions were measured before and after glucose ingestion. In another IGT group, we evaluated the time-course of the skin vascular responses (laser Doppler) to ACh and SNP (by iontophoresis) 1, 2 and 3 h into the OGTT; the plasma glucose profile was then reproduced by means of a variable intravenous glucose infusion and the vascular measurements repeated. Results Following oral glucose, plasma antioxidants were reduced by 5% to 10% (p<0.01) in all patient groups. The response to acetylcholine was not affected by glucose ingestion in any group, while the response to SNP was attenuated, particularly in the IGT group. The ACh:SNP ratio was slightly improved therefore in all groups, even in diabetic participants, in whom it was impaired basally. A time-dependent improvement in ACh:SNP ratio was also observed in skin microcirculation following oral glucose; this improvement was blunted when matched hyperglycaemia was coupled with lower hyperinsulinaemia (intravenous glucose). Conclusions/interpretation Regardless of glucose tolerance, oral glucose does not impair endothelium-dependent vasodilatation either in resistance arteries or in the microcirculation, despite causing increased oxidative stress; the endogenous insulin response is probably responsible for countering any inhibitory effect on vascular function.

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“…22 In addition to the above data, several human studies have clearly shown that acute plasma NEFA elevation leads to increase in BP (Table 1). [23][24][25][26][27] Most of these studies aimed primarily to evaluate the effect of NEFAs on other parameters (i.e. endothelial function) with complicated experiments and are described in detail below, in the sections of the possible pathways linking NEFAs with hypertension.…”

Section: The Effect Of Nefas On Bp Levelsmentioning

confidence: 99%

“…36 In addition to the above findings, elegant in vivo experiments provided detailed information for the effects of NEFAs on endothelial function in humans. Steinberg et al 23 observed that intra-arterial infusion of metacholine in femoral artery of lean healthy individuals during intravenous normal saline infusion resulted in an increase of leg blood flow up to about 300% in relation to baseline levels. After 2 h of systemic administration of either low-or highdose Intralipid and heparin, which both increased plasma NEFA concentration, repeat of metacholine infusion caused a significantly lower increase in leg blood flow than before (maximum increase up to about 200%).…”

Section: Nefa Nitric Oxide and Endothelial Dysfunctionmentioning

confidence: 99%

Non-esterified fatty acids and blood pressure elevation: a mechanism for hypertension in subjects with obesity/insulin resistance?

Sarafidis

Bakris

2006

J Hum Hypertens

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The prevalence of hypertension in individuals with obesity or type II diabetes is substantially elevated. Increased levels of non-esterified fatty acids (NEFAs) in abdominally obese subjects were reported to contribute in the development of various disturbances related to the metabolic syndrome, such as hepatic and peripheral insulin resistance (IR), dyslipidaemia, b-cell apoptosis, endothelial dysfunction and others. However, the involvement of NEFAs in the development of hypertension has been much less studied in comparison to other mechanisms linking IR and central obesity with blood pressure (BP) elevation. This article reviews the existing evidence on the relation between NEFA and hypertension in an attempt to shed a light on it. In vivo data from both animal and human studies support that acute plasma NEFA elevation leads to increase in BP levels, whereas epidemiological evidence suggests a link between increased NEFA levels and hypertension. Further, accumulating data indicate the existence of several pathways through which NEFAs could promote BP elevation, that is a 1 -adrenergic stimulation, endothelial dysfunction, increase in oxidant stress, stimulation of vascular cell's growth and others. The above data support a possible important role of NEFA in hypertension development in patients with obesity and the metabolic syndrome and raise hypotheses for future research.

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Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.

Cited by 701 publications

References 15 publications

Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats

Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

Non-esterified fatty acids and blood pressure elevation: a mechanism for hypertension in subjects with obesity/insulin resistance?

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