Interactions between sympathetic nervous system and endogenous endothelin in patients with essential hypertension

Experimental evidence indicates that endothelin 1 stimulates the sympathetic nervous system by activation of the subtype A receptor. The aim of the present study was to assess whether this mechanism is active in humans and to investigate its potential role in the pathogenesis of essential hypertension. In 15 hypertensive patients and 12 normotensive subjects, blood pressure, heart rate, and muscle sympathetic nerve activity were evaluated during intravenous 20-minute infusion of BQ123 (0.1 mg/kg per hour), an endothelin A receptor antagonist, and sodium nitroprusside (SNP; 0.4 μg/kg per minute). In hypertensive patients, blood pressure was reduced similarly by BQ123 and SNP. In contrast, the increase in muscle sympathetic nerve activity induced by BQ123 (from 52.0±4.9 to 56.8±5.5 bursts per 100 heartbeats; P<0.05 versus baseline) was significantly lower (P<0.05) than that induced by SNP (from 50.6±4.9 to 61.1±5.1 bursts per 100 heartbeats; P<0.05 versus baseline). In normotensive subjects, SNP reduced blood pressure and increased muscle sympathetic activity, whereas BQ123 was ineffective. Thus, in a subgroup (n=9) of normotensive subjects, we administered BQ123 at a higher dose (0.2 mg/kg per hour), representing an equidepressor dose of SNP, inducing a blunted increase in sympathetic activity (from 44.1±2.4 to 50.1±6.4 bursts per 100 heartbeats; P<0.05 versus baseline). Finally, administration of a different vasodilator (papaverine, 0.5 mg/kg per hour) exerted results superimposable to SNP. Endogenous endothelin 1 appears to have a sympathoexcitatory effect both in normotensive and hypertensive subjects through endothelin A receptors, contributing to basal sympathetic vasomotor tone. Moreover, essential hypertension shows an increased susceptibility to the sympathoexcitatory effect of endogenous endothelin 1

Assessing the perceived quality of brachial artery Flow Mediated Dilation studies for inclusion in meta-analyses and systematic reviews: Description of data employed in the development of a scoring tool based on currently accepted guidelines

Brachial artery Flow Mediated Dilation (FMD) is widely used as a non-invasive measure of endothelial function. Adherence to expert consensus guidelines on FMD measurement has been found to be of vital importance to obtain reproducible data. This article lists the literature data which was considered in the development of a tool to aid in the objective judgement of the extent to which published studies adhered to expert guidelines for FMD measurement. Application of this tool in a systematic review of FMD studies © 2016 . (http://dx.doi.org/10.1016/j.atherosclerosis.2016.03.011) (Greyling et al., 2016 [1]) indicated that adherence to expert consensus guidelines is strongly correlated to the reproducibility of FMD data

Effects of wine and grape polyphenols on blood pressure, endothelial function and sympathetic nervous system activity in treated hypertensive subjects

In a randomized double-blind crossover trial, the effect of 8 week supplementation with grape and wine polyphenols on functional and structural vascular parameters and autonomic activity was evaluated in 40 essential hypertensive patients treated with diuretic monotherapy. Ambulatory blood pressure, brachial artery flow mediated dilation (FMD) and pulse-wave velocity (PWV) were measured at baseline and after each 8-week intervention. Forearm resistance artery endothelial function and muscle sympathetic nerve activity (MSNA) response to mental stress and cold-pressor test were measured in two separate sub-groups. No statistically significant differences were found across time or between groups in either blood pressure, FMD, PWV, or resistance artery endothelial function. The MSNA response to the two stressors was non-significantly attenuated after grape-wine polyphenol supplementation. These results do not support the hypothesis that daily consumption of a high dose of grape and wine polyphenols lowers blood pressure or affects vascular function in patients already on antihypertensive medication. © 2016 Elsevier Lt

Recognition in emergency department of septic patients at higher risk of death: Beware of patients without fever

Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of precise guidelines. The aim of this study was to identify the most accurate predictors of in-hospital mortality outcome in septic patients admitted to the ED. Materials and Methods: We compared 651 patients admitted to ED for sepsis (cases) with 363 controls (non-septic patients). A Bayesian mean multivariate logistic regression model was performed in order to identify the most accurate predictors of in-hospital mortality outcomes in septic patients. Results: Septic shock and positive qSOFA were identified as risk factors for in-hospital mortality among septic patients admitted to the ED. Hyperthermia was a protective factor for in-hospital mortality. Conclusions: Physicians should bear in mind that fever is not a criterium for defining sepsis; according to our results, absence of fever upon presentation might be indicative of greater severity and diagnosis of sepsis should not be delayed

Pressure-Corrected Carotid Stiffness and Young's Modulus: Evaluation in an Outpatient Clinic Setting

Background: Conventional measures for assessing arterial stiffness are inherently pressure dependent. Whereas statistical pressure adjustment is feasible in (larger) populations, it is unsuited for the evaluation of an individual patient. Moreover, statistical "correction"for blood pressure may actually correct for: (i) the acute dependence of arterial stiffness on blood pressure at the time of measurement; and/or (ii) the remodeling effect that blood pressure (hypertension) may have on arterial stiffness, but it cannot distinguish between these processes. METHODS: We derived - assuming a single-exponential pressure-diameter relationship - 3 theoretically pressure-independent carotid stiffness measures suited for individual patient evaluation: (i) stiffness index β0, (ii) pressure-corrected carotid pulse wave velocity (cPWVcorr), and (iii) pressure-corrected Young's modulus (Ecorr). Using linear regression analysis, we evaluated in a sample of the CATOD study cohort changes in mean arterial pressure (ΔMAP) and comparatively the changes in the novel (Δβ0, ΔcPWVcorr, and ΔEcorr) as well as conventional (ΔcPWV and ΔE) stiffness measures after a 2.9 ± 1.0-year follow-up. RESULTS: We found no association between ΔMAP and Δβ0, ΔcPWVcorr, or ΔEcorr. In contrast, we did find a significant association between ΔMAP and conventional measures ΔcPWV and ΔE. Additional adjustments for biomechanical confounders and traditional risk factors did neither materially change these associations nor the lack thereof. Conclusions: Our newly proposed pressure-independent carotid stiffness measures avoid the need for statistical correction. Hence, these measures (β0, cPWVcorr, and Ecorr) can be used in a clinical setting for (i) patient-specific risk assessment and (ii) investigation of potential remodeling effects of (changes in) blood pressure on intrinsic arterial stiffness

Inflammatory and Autoimmune Reactions in Atherosclerosis and Vaccine Design Informatics

Atherosclerosis is the leading pathological contributor to cardiovascular morbidity and mortality worldwide. As its complex pathogenesis has been gradually unwoven, the regime of treatments and therapies has increased with still much ground to cover. Active research in the past decade has attempted to develop antiatherosclerosis vaccines with some positive results. Nevertheless, it remains to develop a vaccine against atherosclerosis with high affinity, specificity, efficiency, and minimal undesirable pathology. In this review, we explore vaccine development against atherosclerosis by interpolating a number of novel findings in the fields of vascular biology, immunology, and bioinformatics. With recent technological breakthroughs, vaccine development affords precision in specifying the nature of the desired immune response—useful when addressing a disease as complex as atherosclerosis with a manifold of inflammatory and autoimmune components. Moreover, our exploration of available bioinformatic tools for epitope-based vaccine design provides a method to avoid expenditure of excess time or resources

Adherence to guidelines strongly improves reproducibility of brachial artery flow-mediated dilation.

BACKGROUND: Brachial artery FMD is widely used as a non-invasive measure of endothelial function. Adherence to expert guidelines is believed to be of vital importance to obtain reproducible measurements. We conducted a systematic review of studies reporting on the reproducibility of the FMD in order to determine the relation between adherence to current expert guidelines for FMD measurement and its reproducibility. METHODS: Medline-database was searched through July 2015 and 458 records were screened for FMD reproducibility studies reporting the mean difference and variance of repeated FMD measurements. An adherence score was assigned to each of the included studies based on reported adherence to published guidelines on the assessment of brachial artery FMD. A Typical Error Estimate (TEE) of the FMD was calculated for each included study. The relation between the FMD TEE and the adherence score was investigated by means of Pearson correlation coefficients and multiple linear regression analysis. RESULTS: Twenty-seven studies involving 48 study groups and 1537 subjects were included in the analyses. The adherence score ranged from 2.4 to 9.2 (out of a maximum of 10) and was strongly and inversely correlated with FMD TEE (adjusted R(2) = 0.36, P < 0.01). Use of automated edge-detection software, continuous diameter measurement, true peak diameter for %FMD calculation, a stereostatic probe holder, and higher age emerged as factors associated with a lower FMD TEE. CONCLUSIONS: These data demonstrate that adherence to current expert consensus guidelines and applying contemporary techniques for measuring brachial artery FMD decreases its measurement error

[Chronic inflammation and endothelial dysfunction: analysis of a cohort of patients with SLE and UCTD].

Objective: Cardiovascular complications, mainly caused by an accelerated atherosclerosis, are one of the leading causes of death and disability in patients with systemic autoimmune diseases. Endothelial dysfunction is considered the earliest and reversible step of atherogenesis. Aim of the present study is to investigate endothelial function (EF) in patients with systemic lupus erythematosus (SLE), undifferentiated connective tissue diseases (UCTD) and correlate the results with clinical and laboratory variables. Methods: EF was assessed on the peripheral microcirculation by the perfused forearm technique that can estimate both endothelium- dependent and endothelium- independent vasodilatation. The same evaluation has been repeated in two patients after the administration of 20 mg of 6-metilprednisolone. Results: Twenty-three female patients with SLE or UCTD, with a follow up of at least 1 year have been studied and compared with 8 healthy controls matched for epidemiological variables and traditional risk factors for cardiovascular disease. A significant reduction both in endothelium dependent than endothelium independent vasodilatation was observed in both patients groups compared with controls. In addition, UCTD patients demonstrated a significant reduction in the nitric oxide pathway compared with controls and SLE patients. Finally, steroid administration induced an improvement of vascular reactivity. Conclusions: Despite the well documented side effects of chronic corticosteroid therapy, our data might suggest a role for antinflammatory and immunosuppressive therapy in the prevention of premature atherosclerosis in patients with systemic autoimmune diseases