Oxidative Stress and Vascular Damage in Hypertension: Role of Angiotensin II

Reactive oxygen species are oxygen derivates and play an active role in vascular biology. These compounds are generated within the vascular wall, at the level of endothelial and vascular smooth muscle cells, as well as by adventitial fibroblasts. In healthy conditions, ROS are produced in a controlled manner at low concentrations and function as signaling molecules regulating vascular contraction-relaxation and cell growth. Physiologically, the rate of ROS generation is counterbalanced by the rate of elimination. In hypertension, an enhanced ROS generation occurs, which is not counterbalanced by the endogenous antioxidant mechanisms, leading to a state of oxidative stress. In the present paper, major angiotensin II-induced vascular ROS generation within the vasculature, and relative sources, will be discussed. Recent development of signalling pathways whereby angiotensin II-driven vascular ROS induce and accelerate functional and structural vascular injury will be also considered

Sistemi di rappresentanza tra Stato nazionale e Governo multilivello: un Senato federale per l’Italia

La tesi affronta il problema della rappresentanza politica e la teoria del governo multilivell

Experimental detection of quantum channel capacities

We present an effcient experimental procedure that certifies non vanishing quantum capacities for qubit noisy channels. Our method is based on the use of a fixed bipartite entangled state, where the system qubit is sent to the channel input. A particular set of local measurements is performed at the channel output and the ancilla qubit mode, obtaining lower bounds to the quantum capacities for any unknown channel with no need of a quantum process tomography. The entangled qubits have a Bell state configuration and are encoded in photon polarization. The lower bounds are found by estimating the Shannon and von Neumann entropies at the output using an optimized basis, whose statistics is obtained by measuring only the three observables $\sigma_{x}\otimes\sigma_{x}$, $\sigma_{y}\otimes\sigma_{y}$ and $\sigma_{z}\otimes\sigma_{z}$.Comment: 5 pages and 3 figures in the principal article, and 4 pages in the supplementary materia

Adipocytokine levels mark endothelial function in normotensive individuals

BACKGROUND: Endothelial dysfunction is an independent risk factor for cardiovascular events. Inflammatory mediators released by the adipose tissue can lead to local insulin resistance and endothelial dysfunction. This study addressed the relationship of adipocytokines with endothelial function and blood pressure. METHODS: In 92 newly diagnosed, drug-naïve essential hypertensive patients (HT, mean age 49 yrs) without organ damage and 66 normotensive subjects (NT, mean age 47 yrs), by an automated system, we measured endothelium-dependent and -independent vasodilation as brachial artery flow-mediated dilation before and after administration of glyceryl-trinitrate. Retinol binding protein-4 (RBP4) and resistin levels were determined by ELISA and RIA, respectively. Oxidative stress was evaluated by measuring serum malondyaldehyde (MDA). RESULTS: Flow-mediated dilation was significantly (p = 0.03) lower in HT (5.3 ± 2.6%) than NT (6.1 ± 3.1%), while response to glyceryl-trinitrate (7.5 ± 3.7% vs 7.9 ± 3.4%) was similar. RBP4 (60.6 ± 25.1 vs 61.3 ± 25.9 μg/ml), resistin (18.8 ± 5.3 vs 19.9 ± 6.1 ng/ml) and MDA levels (2.39 ± 1.26 vs 2.08 ± 1.17 nmol/ml) were not different in HT and NT. RBP4 (r = −0.25; p = 0.04) and resistin levels (r = −0.29; p = 0.03) were related to flow-mediated dilation in NT, but not in HT (r = −0.03 and r = −0.10, respectively). In NT, multivariate analysis including RBP4 and confounders showed that only BMI or waist circumference remained related to flow- mediated dilation. In the multivariate model including resistin and confounders, BMI, age and resistin were significantly related to flow-mediated dilation, while only age significant correlated with this parameter when BMI was replaced by waist circumference. CONCLUSIONS: Adipocytokine levels may be independent predictors of endothelial dysfunction in the peripheral circulation of healthy subjects, providing a pathophysiological link between inflammation from adipose tissue and early vascular alterations

Adipocytokine levels mark endothelial function in normotensive individuals

BACKGROUND: Endothelial dysfunction is an independent risk factor for cardiovascular events. Inflammatory mediators released by the adipose tissue can lead to local insulin resistance and endothelial dysfunction. This study addressed the relationship of adipocytokines with endothelial function and blood pressure. METHODS: In 92 newly diagnosed, drug-naïve essential hypertensive patients (HT, mean age 49 yrs) without organ damage and 66 normotensive subjects (NT, mean age 47 yrs), by an automated system, we measured endothelium-dependent and -independent vasodilation as brachial artery flow-mediated dilation before and after administration of glyceryl-trinitrate. Retinol binding protein-4 (RBP4) and resistin levels were determined by ELISA and RIA, respectively. Oxidative stress was evaluated by measuring serum malondyaldehyde (MDA). RESULTS: Flow-mediated dilation was significantly (p = 0.03) lower in HT (5.3 ± 2.6%) than NT (6.1 ± 3.1%), while response to glyceryl-trinitrate (7.5 ± 3.7% vs 7.9 ± 3.4%) was similar. RBP4 (60.6 ± 25.1 vs 61.3 ± 25.9 μg/ml), resistin (18.8 ± 5.3 vs 19.9 ± 6.1 ng/ml) and MDA levels (2.39 ± 1.26 vs 2.08 ± 1.17 nmol/ml) were not different in HT and NT.RBP4 (r = -0.25; p = 0.04) and resistin levels (r = -0.29; p = 0.03) were related to flow-mediated dilation in NT, but not in HT (r = -0.03 and r = -0.10, respectively). In NT, multivariate analysis including RBP4 and confounders showed that only BMI or waist circumference remained related to flow- mediated dilation. In the multivariate model including resistin and confounders, BMI, age and resistin were significantly related to flow-mediated dilation, while only age significant correlated with this parameter when BMI was replaced by waist circumference. CONCLUSIONS: Adipocytokine levels may be independent predictors of endothelial dysfunction in the peripheral circulation of healthy subjects, providing a pathophysiological link between inflammation from adipose tissue and early vascular alterations

The renal resistive index is associated with microvascular remodeling in patients with severe obesity

BACKGROUND Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in obesity, its noninvasive ultrasound assessment still fails to provide pathophysiologic and clinical meaningfulness. We aimed to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity. METHODS We enrolled fifty severely obese patients with an indication for bariatric referring to our outpatient clinic. Patients underwent an extensive reno-metabolic examination, paired with Doppler ultrasound and measurement of the renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L) and vascular response to acetylcholine (ACh), alone or co-incubated with N G -nitro arginine methyl ester (L-NAME), were measured. RESULTS Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower estimated glomerular filtration rate and higher RRI compared to NT, while the presence and extent of albuminuria were similar between the two groups. Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT ( P = 0.042). Multivariable analysis showed a relationship between M/L and RRI ( P  = 0.016, St. β 0.37) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation ( P   =  0.036, St. β = -0.34). Notably, all these correlations were consistent also after adjustment for confounding factors. CONCLUSIONS The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal haemodynamics and microcirculatory disruption

Cholecalciferol administration blunts the systemic renin–angiotensin system in essential hypertensives with hypovitaminosis D:

Introduction: Vitamin D plasma levels are negatively associated with blood pressure and cardiovascular mortality, and vita- min D supplementation reduces cardiovascular events. Renin-angiotensin system (RAS) suppression may be one of the mechanisms involved. However, there are no interventional prospective studies demonstrating a reduction in circulating RAS components after vitamin D treatment. Methods: Fifteen consecutive drug-free patients with essential hypertension and hypovitaminosis D underwent therapy with an oral dose of 25000 I.U. of cholecalciferol once a week for two months, while maintaining a constant-salt diet. In basal conditions and at the end of the study, RAS activity (plasma angiotensinogen, renin, PRA, angiotensin II, aldosterone and urinary angiotensinogen) was investigated, in addition to blood pressure and plasma vitamin D levels (25(OH)D). Results: After cholecalciferol administration, all patients exhibited normalized plasma 25(OH)D values. At the end of the study, a reduction (p < 0.05) in plasma renin and aldosterone, and a decrement, although not significant, of PRA and angiotensin II, was observed. No difference was found in plasma and urinary angiotensinogen or blood pressure values. Conclusions: Our data indicate that in essential hypertensives with hypovitaminosis D, pharmacological correction of vitamin D levels can blunt systemic RAS activity

Early treatment with hydroxychloroquine prevents the development of endothelial dysfunction in a murine model of systemic lupus erythematosus

INTRODUCTION: Accelerated atherosclerosis is one of the major causes of morbidity in patients with systemic lupus erythematosus (SLE). Endothelial dysfunction (ED) is considered an early marker of atherosclerosis. It is a reversible alteration, thus representing an attractive target for prevention strategies against cardiovascular disease. Studies have shown that ED occurs in patients with SLE even in the absence of severe, active disease. Hydroxychloroquine (HCQ) is widely used in SLE to control disease activity, but its use is also associated with an improvement in long-term prognosis. Beyond the beneficial effect in well-established disease, our hypothesis is that treatment with HCQ might have a beneficial impact on ED prevention in SLE. The aim of this study was to assess the impact of early treatment with HCQ on ED in a murine model of SLE. METHODS: Twelve-week-old NZB/W F1 (NZ) and C57BL/6 J mice (controls) were allocated to receive HCQ or vehicle for 6, 12, or 18 weeks. Proteinuria and anti-double-stranded DNA autoantibodies were determined. ED was assessed in mesenteric arteries (pressurized myography). Nitric oxide (NO) availability and reactive oxygen species (ROS) production were evaluated. Vascular ROS production was measured with dihydroethidium (DHE) fluorescent dye. RESULTS: Starting from 18 weeks of age, NZ mice showed a progressive reduction in NO availability, which was normalized by ascorbic acid and apocynin in the up to 24-week-old group, and partly ameliorated in older animals. HCQ administration normalized the NO availability in the up to 24-week-old group, with a partial amelioration in the 30-week-old group. DHE analysis revealed a progressive increment of vascular ROS generation among NZ groups, which was prevented by apocynin. Similarly, in the NZ HCQ-treated group, vascular ROS production was abrogated. CONCLUSIONS: The ED that characterizes this mouse model of SLE is caused by the nicotinamide adenine dinucleotide phosphate oxidase-driven ROS excess. Very early treatment with HCQ is able to exert vascular protection via an antioxidant effect