Fatty Acids Enhance Vascular α-Adrenergic Sensitivity

Stepniakowski, K; Goodfriend, Theodore L.; Egan, Brent M.

doi:10.1161/01.hyp.25.4.774

Cited by 126 publications

(76 citation statements)

References 23 publications

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“…It is probable that the higher FFA concentrations raised blood pressure further by (a) causing more profound endothelial dysfunction in skeletal muscle vasculature, (b) causing endothelial dysfunction in other vascular beds, and/or (c) triggering other pressor forces such as activation of the sympathetic nervous system (13), or the release of endothelium-derived vasoconstrictors. Consistent with this formulation, Stepniakowski et al (14) have shown that elevated circulating FFA levels can increase the sensitivity of the vasculature to pressor agents such as norepinephrine.…”

Section: Discussionmentioning

confidence: 89%

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

Steinberg¹,

Tarshoby²,

Monestel³

et al. 1997

J. Clin. Invest.

701

427

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We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating FFA to levels seen in insulin-resistant subjects can impair endothelial function. We studied leg blood flow responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) or the endothelium-independent vasodilator sodium nitroprusside during the infusion of saline and after raising systemic circulating FFA levels exogenously via a low-or high-dose infusion of Intralipid plus heparin or endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans.

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Section: Discussionmentioning

confidence: 89%

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

Steinberg¹,

Tarshoby²,

Monestel³

et al. 1997

J. Clin. Invest.

701

427

View full text Add to dashboard Cite

show abstract

“…9,30 However, the connection between FFA levels and endothelial function is still debatable. 13,31,32 In a recent study Steinberg et al 33 observed the in¯uence of FFA levels on the endothelium-dependent vasodilation. High FFA levels per se could represent a metabolic disturbance that modi®es the endothelial production of vasoactive substances.…”

Section: Discussionmentioning

confidence: 96%

Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity

et al. 1999

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OBJECTIVE: To ascertain in obesity the role of body fat distribution (the strongest predictor of morbility and mortality in obese subjects) in determining the degree of endothelial dysfunction, an early marker of atherosclerotic disease. SUBJECTS: 18 premenopausal women with uncomplicated obesity excluding other cardiovascular risk factors and 12 age-matched slim healthy women. MEASUREMENTS: Endothelium-dependent vasodilation, studied as diameter variation in response to an increase in shear-stress, was evaluated in the right common femoral artery of obese and slim subjects by a non invasive approach and compared to glyceril-trinitrate vasodilation. To characterize better the vascular functional andaor structural properties, we studied the arterial wall distensibility by an echo-tracking system. Adipose tissue regional distribution was determined by computerised axial tomography. RESULTS: The endothelium-dependent vasodilation was signi®cantly impaired in obese subjects (P`0.005 versus non-obese subjects) while glyceril-trinitrate vasodilation and arterial distensibility were similar in the two groups. In our obese subjects endothelial-dependent vasodilation was inversely correlated to body fat distribution (visceralasubcutaneous adipose tissue ratio: r À0.624, P 0.0058). In contrast, metabolic parameters (except C-peptide response during oral glucose tolerance test (OGTT): r À0.587, P 0.01), blood pressure values and body weight did not correlate with the endothelial function. CONCLUSION: Uncomplicated obesity per se is characterised by an alteration of the endothelial function; the degree of this vascular damage is predicted by body fat distribution independently of body weight and metabolic and other haemodynamic parameters, and correlates with an index of insulin secretion.

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“…Abnormal distribution of FFAs in obese patients has been found to enhance vascular a-adrenergic sensitivity and consequently to increase a-adrenergic tone. 15 The exact mechanisms through which endogenous FFAs exert this effect have not been thoroughly investigated. Lysophospholipids and FFAs inhibit Na + , K + -ATPase and the sodium pump raising vascular smooth muscle tone and resistance.…”

Section: Sympathetic Activation In Obesitymentioning

confidence: 99%

Mechanisms of obesity-induced hypertension

et al. 2010

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The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies. Hypertension Research (2010) 33, 386-393; doi:10.1038/hr.2010.9Keywords: leptin; obesity; pressure natriuresis; rennin-angiotensin-aldosterone system; sympathetic nervous system INTRODUCTION Obesity is a common disorder that develops from the interaction between the genotype and the environment and involves social, behavioral, cultural, physiological, metabolic and genetic factors. A large number of studies have shown that obesity has an important negative impact on health in a population, leading to the recommendation for general practitioners to have an important function in the management of this condition and of its associated comorbidities such as hypertension, hyperlipidemia and hyperinsulinemia/insulin resistance. The relationship between obesity and hypertension is well established both in adults and children. 1,2 Obese individuals exhibit higher levels of office as well as ambulatory blood pressure (BP) from childhood to old age. Obese subjects display higher BP levels than non-obese individuals even in the normotensive range. The combination of obesity, hypertension and other cardiovascular risk factors significantly increases the probability of adverse cardiovascular outcomes, and raises considerations for aggressive treatment strategies. 3 The mechanisms through which obesity directly causes hypertension are still an area of research. Human and animal studies have elucidated the function of adipose tissue derivatives (adipokines and cytokines), neurohumoral pathways, metabolic functions and modulation of pressor/depressor mechanisms. Although obesity-related hypertension may be the result of a combinatio...

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Fatty Acids Enhance Vascular α-Adrenergic Sensitivity

Cited by 126 publications

References 23 publications

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

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

Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity

Mechanisms of obesity-induced hypertension

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