Vascular Generation of Tumor Necrosis Factor-α Reduces Nitric Oxide Availability in Small Arteries From Visceral Fat of Obese Patients

Virdis, Agostino; Santini, Ferruccio; Colucci, Rocchina; Duranti, Emiliano; Salvetti, Guido; Rugani, Ilaria; Segnani, Cristina; Anselmino, Marco; Bernardini, Nunzia; Blandizzi, Corrado; Salvetti, Antonio; Pinchera, Aldo; Taddei, Stefano

doi:10.1016/j.jacc.2011.01.050

Cited by 105 publications

(88 citation statements)

References 32 publications

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“…Part of the study population (14 NT and 14 HT, respectively) was already recruited in previous articles, 15,16 while 27 HT and 28 NT were recruited on purpose for this analysis.…”

Section: Study Populationmentioning

confidence: 99%

Different Impact of Essential Hypertension on Structural and Functional Age-Related Vascular Changes

et al. 2017

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T he endothelium plays a crucial role in acute regulation of vascular tone and in long-term vascular remodeling. In healthy conditions, nitric oxide (NO) is the most important endothelium-derived vasodilator molecule able to inhibit the major key mechanisms promoting the development of atherosclerosis, thus, promoting vascular health.1 NO breakdown by reactive oxygen species (ROS) is the main cause of reduced NO availability and endothelial dysfunction, both in physiological aging and in many pathological conditions, including arterial hypertension.1,2 Hypertension is supposed to induce early vascular aging in different arterial districts. However, vascular features of physiological aging and hypertension are not necessarily similar. With respect to endothelial function, essential hypertensive patients (HT) show a reduced response to acetylcholine (Ach) as compared with normotensive individuals (NT) in each age range. However, with increasing age, vascular response to Ach is similarly reduced among HT and NT. 3,4 Vascular structure changes in the microcirculation represent another hallmark of essential hypertension. 5,6 Increased media to lumen ratio (M/L), which characterizes vascular remodeling, can result from a reduced outer diameter that narrows the lumen without net growth (eutrophic remodeling) or from a thicker media encroaching on the lumen (hypertrophic remodeling). Eutrophic remodeling is most often found in essential hypertension. 7-9 M/L is considered the most reproducible index of small resistance artery structure, 10,11 with a relevant prognostic value, being associated with increased prevalence of cardiovascular events in a high-risk population. 12 Vascular fibrosis is critically important in determining vascular remodeling in hypertension, and it involves, among others, changes in collagen deposition. 13,14 The impact of physiological aging on microvascular structure and the role of vascular fibrosis are still unknown. Therefore, in the present study, we evaluated whether vascular remodeling is physiologically present with advancing age at the level of peripheral small resistance arteries. We also assessed whether the hypertensive disease causes an acceleration of the aging process for vascular function and structure. Collagen deposition as a Abstract-We evaluated whether vascular remodeling is present in physiological aging and whether hypertension accelerates the aging process for vascular function and structure. Small arteries from 42 essential hypertensive patients (HT) and 41 normotensive individuals (NT) were dissected after subcutaneous biopsy. Endothelium-dependent vasodilation (pressurized myograph) was assessed by acetylcholine, repeated under the nitric oxide synthase inhibitor N-nitro-larginine methylester or the antioxidant tempol. Structure was evaluated by media-lumen ratio (M/L). Intravascular oxidative generation and collagen deposition were assessed. Inhibition by N-nitro-l-arginine methylester on ACh was inversely related to age in both groups (P<0.0001) and blunted in HT vers...

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“…Part of the study population (14 NT and 14 HT, respectively) was already recruited in previous articles, 15,16 while 27 HT and 28 NT were recruited on purpose for this analysis.…”

Section: Study Populationmentioning

confidence: 99%

Different Impact of Essential Hypertension on Structural and Functional Age-Related Vascular Changes

et al. 2017

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“…Small arteries were isolated and mounted in a pressurized myograph, as previously described. 11,12 Endothelium-dependent and endothelium-independent relaxations were assessed by cumulative concentrations of acetylcholine (ACh, 0.001-100 μmol/L) and sodium nitroprusside (0.01-100 μmol/L) in vessels precontracted with norepinephrine (1 μmol/L).…”

Section: Preparation Of Small Arteries and Functional Experimentsmentioning

confidence: 99%

“…12 Each segment was analyzed simultaneously after incubation with ascorbic acid (100 μmol/L), DuP-697 (100 μmol/L), SC-560 (100 µmol/L), apocynin (100 μmol/L), DPI (100 μmol/L), allopurinol (100 μmol/L), sepiapterin (100 μmol/L), or Krebs solution.…”

Section: Detection Of Vascular Superoxide Anion Generationmentioning

confidence: 99%

Endothelial Dysfunction in Small Arteries of Essential Hypertensive Patients

et al. 2013

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I n healthy conditions, nitric oxide (NO) acts as a modulator of both vascular tone and structure, playing a predominant protective role on the vasculature. In genetic hypertension, a number of endothelium-derived contracting factors have been identified. These include several prostanoids, such as prostaglandins and thromboxane A 2 , derived from arachidonic acid by the enzyme cyclooxygenase (COX), and reactive oxygen species (ROS), 1,2 generated by several enzymatic sources, including nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase, xanthine oxidase (XO), uncoupled NO synthase (NOS), or COXs itself. 3Pivotal studies in animal models of genetic hypertension have demonstrated an evident production of COX-dependent endothelium-derived contracting factors accounting for endothelial dysfunction. 1,4 In humans, essential hypertensive patients (EH) show a reduced endothelial NO availability in several vascular districts, including peripheral microcirculation. 5In this setting, the infusion of nonselective COX inhibitors normalizes the endothelial function 6,7 and restores NO availability.7 Of note, no additive effects are observed when an antioxidant compound and a COX inhibitor are simultaneously administered in these patients. 8 These findings demonstrate that the COX pathway actively interferes with NO availability and represents a source of ROS in the peripheral microcirculation of EH. At this time, COX represents the unique pathway Abstract-Essential hypertensive patients show a reduced nitric oxide availability secondary to oxidative stress generation in peripheral microcirculation. Cyclooxygenase (COX) contributes to reduce nitric oxide availability.We assessed the possible vascular sources of oxidative stress, including COX-1, COX-2, and nicotinamide adenine dinucleotide phosphate oxidase, as determinants of endothelial dysfunction in small arteries isolated from essential hypertensive patients or normotensive controls. Small arteries were dissected after subcutaneous fat biopsies and evaluated on a pressurized micromyograph. Endothelium-dependent vasodilation was assessed by acetylcholine, repeated under NG-nitro-l-arginine methyl ester, SC-560 (COX-1 inhibitor), DuP-697 (COX-2 inhibitor), ascorbic acid, or the nicotinamide adenine dinucleotide phosphate oxidase inhibitors apocynin or diphenylene iodonium. Vascular oxidative stress generation (fluorescent dihydroethidium), COX-1 and COX-2 expression (Western blot), and localization (immunohistochemistry) were also assessed. In controls, response to acetylcholine was blunted by NG-nitro-l-arginine methyl ester (P<0.001) and unmodified by SC-560, DuP-697, or ascorbic acid. In hypertensive patients, relaxation to acetylcholine was blunted, resistant to NG-nitro-l-arginine methyl ester or SC-560, and enhanced (P<0.01) by DuP-697, apocynin, or diphenylene iodonium (P<0.05). Furthermore, in hypertensive patients, response to acetylcholine was normalized by ascorbic acid or apocynin+DuP-697. Intravascular oxidative stress generation was enhanced in hyp...

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“…Virdis et al (276) compared arteriole function in visceral fat biopsies (obtained during laparoscopic surgery) from 14 severely obese (BMI 48 kg/m 2 ) with 14 nonobese control subjects. Obese subjects had higher plasma and vascular tumor necrosis factor-alpha levels with impaired endothelialdependent relaxation in arterioles that was associated with increased superoxide production and reduced nitric oxide availability.…”

Section: Obesity and Adipose Tissue: Cardiotoxic Effectsmentioning

confidence: 99%

Highlights of the Year in JACC 2011

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et al. 2012

Journal of the American College of Cardiology

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Vascular Generation of Tumor Necrosis Factor-α Reduces Nitric Oxide Availability in Small Arteries From Visceral Fat of Obese Patients

Abstract: Small arteries from visceral fat of obese patients are characterized by an increased TNF-α production, which reduces NO availability by promoting superoxide generation via nicotinamide adenine dinucleotide phosphate oxidase and iNOS activation.

Cited by 105 publications

References 32 publications

Different Impact of Essential Hypertension on Structural and Functional Age-Related Vascular Changes

Different Impact of Essential Hypertension on Structural and Functional Age-Related Vascular Changes

Endothelial Dysfunction in Small Arteries of Essential Hypertensive Patients

Highlights of the Year in JACC 2011

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