Vasodilation Of Brachial Artery Research Articles

The impact of increased daily peanut consumption on indices of peripheral and cerebral vascular function in non-Hispanic Black individuals

Cardiovascular disease, neurocognitive conditions, and cerebral vascular diseases including cognitive impairment, stroke, and Alzheimer’s disease and related dementias disproportionately impact the Non-Hispanic Black (BL) population. The mechanisms are multifactorial but is related to reduced vascular function/health. Our lab, and others, have demonstrated that reduced nitric oxide (NO) bioavailability secondary to oxidative stress, systemic inflammation, and reduced L-arginine bioavailability contributes to reduced vascular function/health in this population. Increased dietary peanut consumption improves various physiological outcomes including blood pressure, cholesterol, type II diabetes, cognitive health, NO bioavailability, and vascular function/health. This improvement is related to increased bioavailability of L-arginine, reduced systemic inflammation, and antioxidant capacity. This study hypothesized that increased daily peanut consumption would improve indices of peripheral and cerebral vascular function/health in a cohort of BL individuals. Methods: Seventeen people participated (11 non-Hispanic White (WH) and 6 BL (age: WH 25±8, BL 21±2; BMI: WH 23±3, BL 22 ± 4; p>0.05 for both). Measures were made before (pre) and after (post) 56 days of daily lightly salted peanut consumption (2 oz/day for females and 3 oz/day for males). Peripheral macro and microvascular function/health was assessed as brachial artery vasodilation (flow mediated dilation, %FMD) and forearm reactive hyperemia (peak mean forearm blood velocity (FBVmean) respectively following 5-min of suprasystolic cuff inflation. Cerebral vascular function/health was assessed as the cerebral vasodilator response during a hypercapnic challenge, i.e., the slope of % cerebral vascular conductance index (CVCi) relative to the change in end-tidal carbon dioxide concentration (ΔPETCO2). Results: There was no effect of race on peripheral macrovascular function assessed as %FMD (WH: 5.3 ±0.89, BL: 6.3 ±1.9 %, p=0.31) or peripheral microvascular function assessed as FBVmean (WH: 82.90 ± 4.5, BL: 72 ± 6.7 cm·s−1, p=0.13). Likewise, there no effect of treatment on %FMD (Pre: 5.4 ± 0.7, Post: 6.2 ± 2.1 %, p=0.46) or FBVmean (Pre: 81.4 ± 6.7, Post: 73.4 ± 8.8 cm·s−1, p=0.27). Lastly, there were no effect of race (WH: 4.0 ± 0.36, BL: 3.9 ± 0.6 %, p=0.85) or treatment (Pre: 3.9 ± 0.56, Post: 4.0 ± 0.39 %, p=0.79) on cerebral vascular function assessed as %CVCi during hypercapnia. Conclusion: The preliminary data suggest that 56 days of increased daily peanut consumption does not induce measurable improvements in indices of vascular function in a cohort of relatively young BL individuals. Future work will continue to assess this effect in a larger cohort of individuals as well as in individuals with existing conditions or diseases (i.e., hypertension, type II diabetes, etc.). Funding: Peanut Institute (982307). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Endogenous Acetylcholine Contributes to Flow-Mediated Dilation in Humans

Background & Objective. Flow-mediated dilation (FMD) is a crucial function of the vascular endothelium wherein intraluminal shear stress stimulates endothelium-dependent vasodilation mediated primarily by nitric oxide. Brachial artery FMD (baFMD) is widely evaluated in clinical research as an index of endothelial function, and impaired baFMD is an independent predictor of cardiovascular risk. Despite the physiological and clinical relevance of FMD, the mechanisms by which shear stress is transduced to endothelium-dependent vasodilation (i.e., upstream of nitric oxide production) remain unclear. baFMD corresponds closely with sensitivity to the endothelium-dependent vasodilator acetylcholine (ACh), and preclinical models suggest ACh is released from endothelial cells in response to shear stress. Therefore, the present study tested the hypothesis that activation of muscarinic ACh receptors facilitates baFMD in humans. Methods. baFMD was evaluated using Doppler ultrasound in healthy participants (n=11; 5F/6M; 23±2 y; means ± SE) under control conditions and following local inhibition of muscarinic ACh receptors via intra-arterial atropine infused proximal to the measurement site. baFMD was assessed in response to transient and sustained shear stimuli in separate trials: 1) reactive hyperemia following 5 min of arterial cuff occlusion (RH-FMD) and 2) steady-state rhythmic handgrip exercise at graded intensities (10, 15, 20, & 25% maximal voluntary contraction, MVC) to produce step increases in shear rate (EX-FMD). Blockade effcacy was confirmed via a dose-response to intra-arterial ACh infusion pre and post atropine. Results. Baseline brachial artery diameter and forearm blood flow were similar in all trials (all P>0.05). Atropine reduced peak brachial artery dilation following cuff release (RH-FMD, Δ diameter, atropine: 4.6±0.8 vs. control: 6.5±0.8%, P=0.04) and increased the shear stimulus (shear rate area under the curve, SRAUC: atropine, 29±3 vs. control: 21±3 s−1×103, P=0.01) such that the percent change in brachial diameter was diminished by 35±16% when normalized to SRAUC (baFMD:SRAUC ratio, atropine: 1.7±0.3 vs. control: 3.9±1.0, P=0.02). Similarly, in the EX-FMD trial, atropine reduced brachial artery diameter at all exercise intensities (25% MVC, percent change in diameter: atropine, 10.8±1.4 vs. control, 15.5±1.7%, P=0.04) despite a greater shear stimulus (shear rate: atropine, 10.9±1.1 vs. control, 9.3±0.9 s−1×102, P=0.01). Thus, atropine reduced the slope describing the relationship between brachial artery vasodilation (percent change) and the change in shear rate by 38±8% across all exercise intensities (slope, atropine: 1.3±0.1 vs. control: 2.4±0.4% Δ×s×10−2, P=0.007). As expected, atropine reduced brachial artery vasodilation in response to upstream infusion of ACh (1.5 μg ACh/dl forearm volume/min, Δ diameter, atropine: 2±1 vs. control: 23±4%, P=0.001). Conclusions. The results suggest endogenous ACh facilitates baFMD in response to both transient and sustained shear stimuli, which highlights a novel physiological role of endogenous ACh in vascular regulation in humans and provides insight regarding the basic mechanisms of flow-mediated vasodilation. NIH R01 HL119337 and F31 HL142240. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Individuals with Post-COVID Conditions Exhibit Delayed Vasodilatory Response following Brachial Artery Occlusion in the Absence of Endothelial Dysfunction and Arterial Stiffness

Background: Post-COVID Conditions (PCC) is a disorder in which individuals who contract the SARS-CoV-2 virus experience prolonged symptoms such as fatigue beyond 4 weeks after initial infection. Preliminary data suggest that individuals who are acutely infected display increased arterial stiffness and endothelial dysfunction, as well as autonomic dysfunction. However, it is not well understood if individuals with PCC continue to experience these dysfunctions beyond acute infection. Therefore, this study aimed to investigate whether vascular and autonomic function are impaired in individuals with PCC compared to individuals without PCC. Methods: Individuals previously infected with the SARS-CoV-2 virus at least 4 weeks prior to participation in the study had vascular and autonomic function assessed at baseline. Individuals experiencing PCC symptoms were classified as symptomatic (SYM, n=12) and individuals without PCC symptoms were classified as asymptomatic (ASYM, n=9). Participants were matched for age (30-55 years) and date since SARS-CoV-2 infection (ranging from 1-12 months). Arterial stiffness (carotid-femoral pulse wave velocity, cfPWV via tonometry), common carotid artery b-stiffness (via ultrasonography and tonometry), and endothelial function (brachial artery flow-mediated dilation, baFMD via ultrasonography) were assessed. Time-to-peak vasodilation (TTP) was assessed from baFMD as the time after cuff release until peak brachial artery dilation. Autonomic function was assessed with spontaneous cardiovagal baroreflex sensitivity (BRS) via sequence technique. Results: At baseline, there were no differences between groups in cfPWV (SYM: 6.2 ± 0.7 m/s, ASYM: 6.3 ± 1.1 m/s; p=0.90), baFMD (SYM: 7.3 ± 6.1%, ASYM: 7.7 ± 5.6%; p=0.87), brachial artery baseline diameter (SYM: 3.4 ± 0.6 mm, ASYM: 3.2 ± 0.4 mm; p=0.37) and common carotid b-stiffness index (SYM: 9.2 ± 2.1U, ASYM: 8.2 ± 2.5U; p=0.360). Despite no differences in baFMD% between groups, the SYM group had a significantly higher baseline baFMD TTP compared with the ASYM group (SYM: 61.6 ± 23.1 s, ASYM: 36.8 ± 14.3 s; p=0.010). There were no significant differences in cardiovagal BRS (SYM: 10.9 ± 6.8 ms/mmHg, ASYM: 11.8 ± 2.6 ms/mmHg; p=0.80). Conclusions: While arterial stiffness, endothelial function and baroreflex function did not differ between groups, individuals with PCC did present with delayed peak brachial artery vasodilation in response to shear stress. These data suggest any possible effects on vascular and autonomic function from acute SARS-CoV2 infection appear to be resolved beyond 4 weeks in those who experience prolonged symptoms. However, the delayed vasodilatory response may indicate some level endothelial dysfunction that persists in individuals with PCC. Funded by: Russell B. Day and Florence D. Day Chair in Liberal Arts and Sciences fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of acute heparin administration on glycocalyx thickness and endothelial function in healthy younger adults.

The endothelial glycocalyx is a dynamic, gel-like layer that is critical to normal vascular endothelial function. Heparin impairs the endothelial glycocalyx and reduces vascular endothelial function in a murine model; however, this has yet to be tested in healthy humans. We hypothesized that a single bolus dose of heparin would increase circulating glycocalyx components and decrease endothelial glycocalyx thickness resulting in blunted brachial artery vasodilation in healthy younger adults. Healthy adults (n = 19, aged 18-39 yr, 53% female) underwent measurements of the endothelial glycocalyx and vascular endothelial function at baseline and after a single bolus 5,000 U dose of heparin. The glycocalyx components syndecan-1 and heparan sulfate were measured from plasma samples using enzyme-linked immunosorbent assays. Glycocalyx thickness was determined as perfused boundary region (PBR) in sublingual microvessels using the GlycoCheck. Endothelial function was measured via ultrasonography and quantified as brachial artery flow-mediated dilation (FMD). Following acute heparin administration, there was no increase in syndecan-1 or heparan sulfate (P = 0.90 and P = 0.49, respectively). In addition, there was no change in PBR 4-7 µm (P = 0.55), PBR 10-25 µm (P = 0.63), or 4-25 µm (P = 0.49) after heparin treatment. Furthermore, we did not observe a change in FMDmm (P = 0.23), FMD% (P = 0.35), or plasma nitrite concentrations (P = 0.10) in response to heparin. Finally, time to peak dilation and peak FMD normalized to shear stress were unchanged following heparin (P = 0.59 and P = 0.21, respectively). Our pilot study suggests that a single bolus intravenous dose of heparin does not result in endothelial glycocalyx degradation or vascular endothelial dysfunction in healthy younger adults.NEW & NOTEWORTHY The endothelial glycocalyx's role in modulating vascular endothelial dysfunction with aging and disease is becoming increasingly recognized. This study presents novel findings that acute heparin administration is not a feasible method to experimentally degrade the endothelial glycocalyx and measure concurrent changes in vascular endothelial function in healthy humans. Alternative approaches will be needed to translate findings from preclinical studies and test the effects of acute endothelial glycocalyx degradation on vascular endothelial function in humans.

Effect of diabetes duration on subclinical target organ damage in young diabetic adults with type 1 diabetes mellitus

Abstract Objective and aim Cardiovascular disease is a key cause of premature mortality in type 1 diabetes mellitus (DMt1). According to ESC guidelines, 10-year risk of death from cardiovascular disease in 35-year-old patients with diabetes lasting ≤10 years is estimated as moderate, however studies based on the young adult patients with DMt1 are limited. The aim of this study is to identify the relationship between the duration of DMt1 and occurrence of subclinical cardiovascular target organ damage among adult patients before the age of thirty. Material and methods We included patients aged from 18 to 30 years old with childhood- or juvenile-onset diabetes mellitus type 1. In all patients 24-hour blood pressure measurement was performed and a daily pressure profile (dipper or non-dipper) was defined. Non-invasive diagnostics of subclinical cardiovascular damage included: • 2-dimensional echocardiographic examination with the assessment of global longitudinal strain (GLS), • ultrasound of the carotid arteries with the assessment of intima media thickness (IMT), • assessment of the pulse wave velocity (PWV), • assessment of flow-dependent brachial artery vasodilation (FMD), • assessment of the ankle-brachial index (ABI). Results Obtained from non-invasive examination were compared between two groups depending on duration of DMt1: group 1 ( DMt1 lasting ≤10 years) vs group 2 (DMt1 lasting >10 years). Results The study population consist of 56 patients (48% male). Group consist of 25 patients and group 2 consist of 31 patients. Statistical analysis showed that received values of GLS (P=0.04) and PWV (P=0.01) differ significantly between group 1 and group 2. Interestingly the GLS, but not PWV, showed a significant negative linear correlation with the duration of diabetes (r=0.28; P=0.03). A post-hoc analysis showed that among patients with a DMt1 duration of ≤10 years absolute GLS values were significantly lower in patients with non-dipper profile than those with a dipper profile (P=0.04) (Fig. 1). Also a post-hoc analysis demonstrated significant difference in IMT thickness among non-dipping patients according to time of DMt1 duration (P=0.01) (Fig. 1). Conclusions Subclinical target organ damage can be detected even in young adults with DMt1 (aged 18-30 years). Patients with DMt1 lasting >10 years had a significantly lower absolute GLS value and GLS value correlate with the duration of diabetes. Patients with DMt1 lasting >10 years had a significantly higher PWV value.Fig 1. Post-hoc analysis of GLS and IMT

#3145 ASSOCIATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISM WITH ENDOTHELIAL DYSFUNCTION IN DIABETIC NEPHROPATHY AMONG AZERBAIJANIS

Abstract Background and Aims Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the endothelial cells of blood vessels has been suggested as playing an important role in the pathogenesis of Diabetic nephropathy (DN). It regulates endothelial function and maintains endothelial-dependent vasodilation in multiple organs, including the kidney. The study was carried out to investigate the association of T-786C single nucleotide polymorphisms with the flow mediated dilation (FMD) in DN among type 2 diabetic subjects. Method 90 patients (45 male and 45 female) with diabetic nephropathy were recruited from Nephrology and Endocrinology departments of the Azerbaijan Medical University hospital. As a control group the results were compared with the findings in 100 healthy Azerbaijani individuals (50 males and 50 females). The study was approved by ethics committee and informed consent was obtained from all patients in written form. Brachial endothelial function was determined by brachial artery vasodilator response or brachial FMD in the dominant arm according to previously validated techniques. T786C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism analysis. Results The results showed significant differences between DN group and control group regarding the genotype and allele distributions of the T786C single nucleotide polymorphisms. The CC genotype was significantly more frequent in diabetics nephropathy patients than in control group (42% vs. 8%, p = 0.01). FMD in allele homozygote T786C(TT), T786C(CC) and heterozygote T786C(CT) were respectively 13.5 ±0.16%, 12.3±0.19%,13.9 ±0,28%. In the study groups, Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS. Subjects with the 786C(CC) (n = 48) showed significantly reduced FMD with those with T786C (TT) (n = 7) (p = 0.021) and T786C (CT) (n = 35) (p = 0.023), whereas there was no significant difference in endothelial-independent vasodilation between these groups. Although subjects with homozygote T786C(TT), did not show significantly reduced levels of FMD. Who were carriers of the T786C allele demonstrated markedly reduced levels of FMD compared with noncarriers (p = 0.019). Conclusion The data suggest that in diabetic nephropathy, the eNOS T786C allele may be involved in endothelial dysfunction. Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS.

ENDOTHELIAL FUNCTIONAL STATUS IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES MELLITUS AFTER COVID-19

Objective: Aim of the study was to estimate endothelial functional status in patients with hypertension and type 2 diabetes mellitus (T2DM) who underwent Covid-19. Design and method: 56 patients with hypertension and T2DM after coronavirus infection (Group I) and 56 patients with hypertension and T2DM without any history of Covid-19 (Group II) were enrolled in this study. Group I patients aged 43-75 years, mean age 62.4±12.5 years; male = 46% and Group II patients aged 42-77 years, mean age 63.6±13.7 years; male = 43%. Endothelial functional status was assessed by flow-mediated vasodilation of brachial artery (FMD). All statistical analysis were performed by SPSS 26.0 software. Results: FMD of brachial artery was significantly decreased in patients with hypertension and T2DM after Covid-19 than those patients without Covid-19 (P<0.01). There were a correlation between Covid-19 and reduced FMD in Group I (r = 0.7, CI 95%, P = 0.032). When we assessed systolic function of the left ventricle, there were a positive correlation between reduced FMD and low ejection fraction (r = 0.6, CI 95%, P = 0.028), however this correlation were more pronounced in Group I (P = 0.001). Multivariate analysis revealed that reduced flow-mediated vasodilation of brachial artery was independent predictor of poor systolic function of patients with hypertension and T2DM especially in those after Covid-19 (odds ratio [OR] 1.52, P = 0.026). When we separately analyzed between men and women there were not any statistical significant changes between male and female (P>0.05). Conclusions: Patients with hypertension and type 2 diabetes mellitus after Covid-19 had impaired FMD of brachial artery. Even though, there were positive correlation between flow-mediated vasodilation of brachial artery and reduced ejection fraction, patients with hypertension and T2DM after Covid-19 had strong correlation of it. In hypertensive patients with type 2 diabetes mellitus who have undergone Covid-19, FMD independently associated with poor left ventricular systolic function.

A study of the relationship between brachial artery vasodilation and platelet/lymphocyte ratio in diabetic patients with coronary atherosclerosis.

To investigate the correlation between brachial artery flow-mediated endothelium-dependent dilation (FMD) and platelet-lymphocyte ratio (PLR) in peripheral blood and coronary atherosclerosis in diabetic patients. Seventy-five diabetic patients aged 62 ± 9 years, 68% male and 32% female, who underwent brachial artery endothelial function test and coronary CT scan were collected. Coronary artery calcification (CAC) was observed to assess the presence of coronary atherosclerosis, and high-resolution extravascular ultrasound was used to detect FMD. Platelet count and lymphocyte count were recorded by routine blood tests, and PLR was calculated for each study subject. Statistical methods were used to verify the association of FMD and PLR with CAC assessed by CT, respectively. Patients with coronary atherosclerosis had decreased FMD and increased PLR compared with patients with normal coronary arteries. Univariate logistic regression analysis showed that CAC score was significantly associated with both FMD (odds ratio: 0.167; 95% confidence interval: 0.049-0.565; p = 0.002) and PLR (odds ratio: 0.127; 95% confidence interval: 0.033-0.484; p = 0.001) at FMD < 5.1% or PLR > 130. The area under the ROC curve of FMD and PLR alone was 0.760 and 0.763, respectively. In addition, combined diagnosis of FMD and PLR showed the highest area under the ROC curve (0.830). FMD combined with PLR is expected to be a precise diagnostic modality for coronary artery calcification in diabetic patients.

Evaluation of Circulating Platelet Extracellular Vesicles and Hypertension Mediated Organ Damage.

Elevated circulating platelet-derived extracellular vesicles (pEVs) have been associated with arterial hypertension. The role of hypertension-mediated organ damage (HMOD) to induce EV release is still unknown. We studied the micro- and macro-vascular changes (retinal vascular density and pulse wave velocity), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), and assessed the psychosocial status (anxiety and depression) in hypertensive patients to determine their relationship with EV release. Pulse wave velocity showed a significant positive correlation with pEVs (r = 0.33; p = 0.01). Systolic blood pressure (SBP) negatively correlated with retinal vascularity. The superficial retinal vascular plexus density in the whole image showed a significant negative correlation with 24 h SBP (r = −0.38, p < 0.01), day-SBP (r = −0.35, p = 0.01), and night-SBP (r = −0.27, p = 0.04). pEVs did not show significant associations with microvascular damage (retinal vascular density), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), or psychosocial status (anxiety and depression). Our results indicate that the pEV levels were associated with macrovascular damage measured by PWV, whereas no significant association between pEVs and microvascular damage, endothelial function, or emotional status could be detected. The potential utility of pEV in clinical practice in the context of HMOD may be limited to macrovascular changes.

Persistent vascular dysfunction following an acute nonpharmacological reduction in blood pressure in hypertensive patients.

Vascular dysfunction, an independent risk factor for cardiovascular disease, often persists in patients with hypertension, despite improvements in blood pressure control induced by antihypertensive medications. As some of these medications may directly affect vascular function, this study sought to comprehensively examine the impact of reducing blood pressure, by a nonpharmacological approach (5 days of sodium restriction), on vascular function in 22 hypertensive individuals (14 men/8 women, 50 ± 10 years). Following a 2-week withdrawal of antihypertensive medications, two 5-day dietary phases, liberal sodium (liberal sodium, 200 mmol/day) followed by restricted sodium (restricted sodium, 10 mmol/day), were completed. Resting blood pressure was assessed and vascular function, at both the conduit and microvascular levels, was evaluated by brachial artery flow-mediated dilation (FMD), reactive hyperemia, progressive handgrip exercise, and passive leg movement (PLM). Despite a sodium restriction-induced fall in blood pressure (liberal sodium: 141 ± 14/85 ± 9; restricted sodium 124 ± 12/79 ± 9 mmHg, P < 0.01 for both SBP and DBP), FMD (liberal sodium: 4.6 ± 1.8%; restricted sodium: 5.1 ± 2.1%, P = 0.27), and reactive hyperemia (liberal sodium: 548 ± 201; restricted sodium: 615 ± 206 ml, P = 0.08) were not altered. Similarly, brachial artery vasodilation during handgrip exercise was not different between conditions (liberal sodium: Δ0.36 ± 0.19 mm; restricted sodium: Δ0.42 ± 0.18 mm, P = 0.16). Lastly, PLM-induced changes in peak blood flow (liberal sodium: 5.3 ± 2.5; restricted sodium: 5.8 ± 3.6 ml/min per mmHg, P = 0.30) and the total vasodilatory response [liberal sodium: 2 (0.9-2.5) vs. restricted sodium: 1.7 (1.1-2.6) ml/min per mmHg; P = 0.5] were also not different between conditions. Thus vascular dysfunction, at both the conduit and microvascular levels, persists in patients with hypertension even when blood pressure is acutely reduced by a nonpharmacological approach.

Acute Effect of Intermittent Hypoxia on Peripheral Vascular Function in Young Healthy Adults

Continuous exposure to hypoxia elicits a chemoreceptor‐mediated increase in sympathetic nerve activity and a simultaneous peripheral vasodilation due to an increase in nitric oxide production. The aim of the present study was to determine whether short, repeated bouts of hypoxia induce brachial artery vasodilation and acutely improve endothelial function. Ten young healthy adults (4 women, age: 24±3 years, height: 176±9 cm, body weight: 80±13 kg) visited the laboratory on two separate occasions. Endothelium‐dependent vasodilation was assessed by brachial artery flow‐mediated dilation using a semiautomated diagnostic ultrasound system before and after exposure to either intermittent hypoxia (IH) or intermittent normoxia (IN). Intermittent hypoxia consisted of eight 4‐min hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with breathing room air to resaturation, and intermittent normoxia consisted of eight 4‐min normoxic cycles separated by one minute of breathing room air. Air was made hypoxic by titrating nitrogen into a breathing circuit. Brachial artery diameter was assessed via ultrasound throughout the protocols. Hemodynamics, arterial oxygen saturation, and pulmonary gas exchange were also continuously assessed during the protocols. By design, intermittent hypoxia resulted in an arterial oxygen saturation of 81±2%, corresponding to oxygen levels of 11.9±2.2%. Exposure to intermittent hypoxia, but not intermittent normoxia, elicited a brachial artery vasodilation (IH: 0.38±0.06 to 0.40±0.06 vs. IN: 0.38±0.06 to 0.38±0.06 cm, p&lt;0.01). However, neither intermittent hypoxia nor intermittent normoxia acutely affected brachial artery flow‐mediated dilation (IH: 5.8±1.9 to 5.3±1.6% vs. IN: 6.1±2.4 to 6.5±1.7%, p=0.96). Intermittent hypoxia increased cardiac output (5.2±0.9 to 5.9±1.4 L·min‐1, p=0.03) mainly due to an increase in heart rate (57±9 to 68±11 bpm, p&lt;0.01). In conclusion, exposure to intermittent hypoxia triggered a brachial artery vasodilation but did not affect endothelium‐dependent vasodilation in young healthy adults. Multiple sessions of intermittent hypoxia may be necessary to improve nitric oxide synthesis and endothelial function.

Tetrahydrobiopterin Administration Augments Exercise-Induced Hyperemia and Endothelial Function in Patients With Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare, auto-immune disease with variably progressive fibrosis of the skin and internal organs, as well as vascular dysfunction. Recently, we demonstrated a decrement in exercising skeletal muscle blood flow and endothelium-dependent vasodilation in SSc, but the mechanisms responsible for these impairments have not been investigated. Thus, we sought to determine if acute administration of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase (eNOS), would improve hyperemia and brachial artery vasodilation during progressive handgrip exercise in SSc. Thirteen patients with SSc (63 ± 11 years) participated in this placebo-controlled, randomized, double-blind, crossover study. Tetrahydrobiopterin (10 mg/kg) administration resulted in a ~4-fold increase in circulating BH4 concentrations (P < 0.05). Cardiovascular variables at rest were unaffected by BH4 (P > 0.05). During handgrip exercise, BH4 administration increased brachial artery blood flow (placebo: 200 ± 87; BH4: 261 ± 115 ml/min; P < 0.05) and vascular conductance (placebo: 2.0 ± 0.8; BH4: 2.5 ± 1.0 ml/min/mmHg; P < 0.05), indicating augmented resistance artery vasodilation. Tetrahydrobiopterin administration also increased brachial artery vasodilation in response to exercise (placebo: 12 ± 6; BH4: 17 ± 7%; P < 0.05), resulting in a significant upward shift in the slope relationship between Δ brachial artery vasodilation and Δ shear rate (placebo: 0.030 ± 0.007; BH4: 0.047 ± 0.007; P < 0.05) that indicates augmented sensitivity of the brachial artery to vasodilate to the sustained elevations in shear rate during handgrip exercise. These results demonstrate the efficacy of acute BH4 administration to improve both resistance and conduit vessel endothelial function in SSc, suggesting that eNOS recoupling may be an effective strategy for improving vasodilatory capacity in this patient group.

Endothelial function status in hypogonadal men

Background: Type 2 diabetes mellitus (T2DM) and hypogonadism are mutually aggravating diseases associated with the development and progression of cardiovascular pathology. The status of endothelial function in men with T2DM and hypogonadism hasn’t been studied.Aims: To assess the effect of hypogonadism on endothelial function in men with T2DM.Materials and methods: Patients underwent clinical studies, assessment of carbohydrate and lipid metabolism, the content of sex hormones (total testosterone (T), sex hormones binding globulin, free T, luteinizing hormone) and markers of endothelial function (nitric oxide (NO), endothelial nitric oxide synthase type 3 (eNOS3), endothelin, adhesion molecules ICAM-1, VCAM-1, p- and e-selectins, cadherin), ultrasound examinations of endothelium-dependent vasodilation (EDVD) of the brachial artery (BA) and carotid arteries with an assessment of the thickness of intima-media complex (TIM) were performed.Results: The study included 276 men with T2DM (age 54.0[49;60] years), who were divided into 2 groups: 1–124 patients with hypogonadism; 2–152 eugonadal patients. Reduction of the endothelial vasomotor function was detected in 32.4% of patients in the 2st group and in 55.3% of the 1nd group (χ2=6.1; p=0.01), which was associated with a decrease in EDVD by 29.8 % (p&lt;0.001) and an increase in the time of development of maximal BA vasodilation by 30 seconds in patients with hypogonadism (p&lt;0.001). The TIM of the carotid arteries was 10% more in group 1 compared with group 2 (p=0.03). The ­level of NO in the 1st group was reduced by 1.6 times (p=0.001), eNOS3–by 1.5 times (p=0.038) compared with the 2nd group. The concentrations of adhesion molecules were higher in group 1 compared to group 2: VCAM-1 by 32.5% (p&lt;0.001), ICAM-1 by 43.5% (p&lt;0.001), p-selectin–by 19.3% (p=0.004), cadherin–6 times (p&lt;0.001).Conclusion: Hypogonadism in men with T2DM is associated with the development of endothelial dysfunction, which manifests in a weakening of the EDVD and a slowdown in its development, as well as disturbances of the secretory activity of endothelium–a decrease in NO synthesis and activation of the adhesion molecules expression, which can be regarded as an universal pathogenetic mechanism of the development of cardiovascular diseases in combination of T deficiency and T2DM.

Serum sclerostin in acute kidney injury patients

BackgroundMany of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI. ObjectiveWe looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome. Cases and methodsThis is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away. ResultsSerum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P<0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. Survivors were younger in age (median 55.5 vs. 60 years, P<0.04), had lower AST (30.5 vs. 58 units, P<0.001), had higher platelet count (206 vs 162×109/L, P<0.001), otherwise, there was no significant difference in any of the other parameters between survivors and patients that were lost. Serum sclerostin had strong correlation with FGF23 in group I (r=0.99, P<0.001) and group II (r=1, P<0.001). Homa IR had positive correlation with serum sclerostin (r=0.148, P=0.014) and serum FGF23 (r=0.142, P=0.018) in group I. ConclusionSclerostin is intimately related to FGF23. Sclerostin level increases in AKI patients. Both sclerostin and FGF23 might increase insulin resistance but have no impact on FMD. Neither sclerostin nor FGF23 interfere with AKI outcome.

Indicators of ambulatory blood pressure monitoring in patients with essential hypertension of the 2-nd stage depending on the type of 24-hours blood pressure profile, the state of the left ventricular diastolic filling and endothelial function of vessels

Annotation. Arterial hypertension (AH) is one of the most important risk factors for the development of cardiovascular complications and mortality in the world and it has become a medical and social problem. The prevalence of hypertension will increase to 1.56 billion by 2025, making the disease a very serious problem. The severity of clinical manifestations and prognosis in patients with hypertension are determined not only by the degree of increase in blood pressure (BP) but also the damage to target organs. The load on the cardiovascular system caused by elevated BP leads to structural remodelling of the heart and vessels. The aim – to evaluate peculiarities of indicators of ambulatory blood pressure monitoring in patients with essential hypertension of the 2nd stage depending on the type of 24-hours blood pressure profile, the state of the left ventricular diastolic filling and endothelial function of the vessels and determine independent clinical and instrumental criteria of the 24-hours profile “dipper” and “non-dipper”. The study involved 110 patients (40 men and 70 women) with hypertension of the II-nd stage, hypertensive heart, chronic heart failure of the 0-I stage (average age was 54.19±0.89 years). The patients underwent 24-hour blood pressure monitoring, echocardiography and determination the thickness of the intima-media complex (IMCT) of the brachial artery, endothelium-dependent (EDVD) and endothelium-independent (EIVD) vasodilatation. For statistical analysis, arithmetic means (M), errors of mean values (m), t - Student's t test for paired measurements were calculated. Correlation ratios were evaluated by the method of linear correlation for parametric data and the method of Spearman’s rank correlation for nonparametric data. Paired group comparisons were performed by the nonparametric Mann-Whitney method. Wilcoxon test was used in the analysis of dependent samples. Step-by-step multifactor regression was used to identify independent criteria for daily blood pressure profiles. Two types of 24-hours profile of blood pressure – “dipper” and “non-dipper” were detected. The left ventricle diastolic dysfunction (LVDD) by type of relaxation disorder was observed in all “non-dipper” patients and most “dipper” patients. Patients with DD had higher levels of BP per 24-hours, day, night, corresponding the time indexes, the magnitude of the morning increase of systolic and diastolic blood pressure, more pronounced structural changes of the heart and vessels compared with patients with preserved diastolic filling of the LV(р&lt;0,01). The duration of the hypertensive anamnesis (p=0.0002), the thickness of the posterior wall of the LV (p=0.002), the maximum speed of early diastolic filling of the LV (E) (p&lt;0.0001), the LV ejection fraction (p=0.001), the index of the left atrium (p=0.008), the thickness of the intima-media complex of the brachial artery (p=0.013), increase of the diameter of the brachial artery in 90 s after compression (EDVD) (p&lt;0.0001) and in 5 min after taking of nitroglycerin (EIVD) (p=0.009) were determined as independent clinical and instrumental criteria of the “dipper” and “non-dipper” profile. Insufficient the degree of the nightly decrease of the BP, higher magnitude of the morning increase of systolic and diastolic BP cause more hemodynamic pressure on target organs and lead to more significant pathological remodeling of the LV and vessels, disorders of the LV relaxation processes and endothelial dysfunction.

Relationship between the volume of perivascular adipose tissue and the vascular wall lesion

Aim. To study the relationship between the volume of perivascular adipose tissue (PVAT) and the vascular wall lesion.Material and methods. The study included 318 patients without cardiovascular disease (mean age, 63,5±13,7 years). Hypertension was detected in 268 (84,3%) patients. All patients underwent assessment of anthropometric characteristics, lipid profile, arterial wall stiffness with the estimation of cardio-ankle vascular index, intima-media thickness, brachial artery endothelial vasomotor function. Chest computed tomography was performed with the estimation of the volumes of PVAT and pericardial adipose tissue (PAT).Results. The volume of PVAT, on average, was 0,3 [0,2; 0,4] cm3 . The VAT volume was significantly higher in obese individuals when compared with patients with normal body weight: 0,4 [0,3; 0,5] vs 0,25 [0,2; 0,4] cm3 (p=0,0007). The VAT volume was higher in individuals with an increased CAVI level when compared with patients with normal CAVI values: 0,4 [0,3; 0,5] vs 0,3 [0,25; 0,3] (p=0,02). A significant correlation was found between the VAT volume and body mass index (r=0,27, p&lt;0,005), waist circumference (r=0,41, p&lt;0,005), CAVI (r=0,49, p&lt;0,05), impaired endothelium-dependent brachial artery vasodilation (r=0,38, p&lt;0,05). When performing multiple linear regression, a significant relationship of CAVI was found with age (β±SE, 0,51±0,15; p=0,002) and volume of PVAT (β±SE, 0,41±0,13; p=0,005).Conclusion. The results indicate the relationship of PVAT with visceral obesity and vascular wall stiffness parameters.

Abstract 13944: Young, Non-Hispanic Black Males and Females Exhibit Divergent Peripheral and Cerebral Vascular Reactivity

Introduction: In the U.S., cardiovascular and cerebrovascular diseases (CVD) remain more prominent in non-Hispanic black individuals than in other populations. Across most racial/ethnic groups, total CVD prevalence is ~10% lower in females; however, total CVD prevalence in black females (BF) is similar to that of black males (BM). Conversely, BM have ~23% higher age-adjusted stroke mortality compared to BF, a pattern not seen in other groups. While the mechanisms behind these race-by-sex differences are multifactorial, vascular dysfunction likely contributes. Our group and others have demonstrated reduced brachial artery and cerebrovascular vasodilation in black versus white individuals, though much of this work did not specifically address sex differences. To this end, we have recently investigated and reported divergent mechanisms of reduced cutaneous microvascular function in BM and BF; however, more work is needed to better understand whether such findings extend to other vascular regions. Hypothesis: We tested the hypothesis that BF and BM would have divergent degrees of reduced peripheral and cerebral vasodilator responsiveness. Methods: Eleven BF and 15 BM (22 ± 4 vs. 23 ± 3 yrs) underwent testing for brachial artery flow-mediated dilation (FMD; conduit artery function) and post-occlusive reactive hyperemia (PORH; microvascular function), along with cerebrovascular reactivity (CVR) to rebreathing-induced hypercapnia. Results: FMD was greater in BF versus BM (9.10 ± 3.49 vs. 5.84 ± 2.78%; P = 0.02), even when normalized to baseline diameter or shear rate ( P &lt; 0.05 for both). BF had similar PORH when assessed as peak blood velocity (77.1 ± 19.9 vs. 79.4 ± 19.6 cm • s -1 ; P &gt; 0.05) but lower peak blood flow (343.6 ± 169.8 vs. 495.4 ± 196.9 mL/min; P &lt; 0.05) and blood flow AUC (133.6 ± 61.1 vs. 220.3 ± 130.7 mL; P = 0.04) relative to BM. CVR was greater in BF versus BM (0.024 ± 0.010 vs. 0.012 ± 0.006 cm • s -1 • mmHg -1 • mmHg -1 ; P &lt; 0.01). Conclusion: These data suggest that young, BM have lower vascular reactivity than BF during some, but not all, tests of vascular function. More work in this area is needed to better understand the potential biological and social mechanisms influencing sex differences in vascular function and CVD risk in black individuals.

Effect of testosterone on endothelial function in men with type 2 diabetes mellitus

Objective: to study the effect of testosterone (T) levels on laboratory and instrumental markers of endothelial dysfunction (ED). Materials and methods: the study included 276 male patients with type 2 diabetes mellitus (DM). General clinical studies were carried out, analysis of parameters of carbohydrate metabolism, the content of hormones (total T, SHBG, free T, estradiol, LH, FSH, prolactin, TSH, DHEA) were performed. Endothelial secretory function was assessed using markers such as: nitric oxide (NO), endothelial NO synthase type 3, endothelin, ICAM-1, VCAM-1, p- and e-selectins, cadherin, PAI-1, VEGF-1. Additionally, the content of biologically active substances affecting endothelial function was studied: homocysteine B, C-reactive protein (CRP), osteoprotegerin, leptin, resistin, adiponectin. The vasomotor function of the endothelium was assessed by ultrasound examination of the endothelium-dependent vasodilation (EDVD) of the brachial artery (BA) during the reactive hyperemia test; in addition, the thickness of the intima-media complex (TIM) of the carotid arteries was measured. Correlation analysis was performed using Spearman’s method. Results: the level of total T is interrelated with the instrumental parameters of the endothelial function: the TIM of the carotid arteries (r = -0.26; p = 0.009), the time of maximum BA vasodilation development (r = -0.41; p &lt;0.001), EDVD (r = 0 , 28; p = 0.004), as well as laboratory markers of ED: ICAM-1 (r = -0.45; p &lt;0.001), VCAM-1 (r = -0.29; p &lt;0.001), cadherin (r = -0.36; p &lt;0.001), NO (r = 0.32; p = 0.002), VEGF (r = -0.23; p = 0.001), CRP (r = -0.29; p &lt;0.001) and adipohormones: leptin (r = -0.26; p = 0.01), resistin (r = -0.24; p &lt;0.001) and adiponectin (r = 0.28; p = 0.007). Conclusion: T deficiency is associated with a deterioration in the vasomotor function of the endothelium: a decrease in EDVD along with an increase in the time of maximum BA vasodilation development and impaired endothelial secretory function: an increase in the concentrations of VCAM-1, ICAM-1, cadherin, VEGF and, on the contrary, a decrease in NO levels. A decrease in T levels is accompanied by an increase in the content of CRP, resistin, leptin and a decrease in adiponectin, which aggravates the dysfunction of the endothelium.

STUDY OF VASCULAR ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract. Currently, inflammatory bowel disease (IBD) is the most complex and not fully resolved problem in modern gastroenterology. IBD, with its two main subtypes, Crohn's disease (CD) and ulcerative colitis (UC), is a complex multifactorial pathology caused by external and internal factors, including host genetics, the immune system, environmental factors, and the gut microbiome. The possible involvement of endothelial dysfunction is also discussed. There is evidence that in diseases characterized by chronic systemic inflammation, it affects the properties of the arteries and causes both endothelial dysfunction and changes in arterial stiffness. The aim is to study the functional state of the vascular endothelium in patients with inflammatory bowel diseases. Material and methods. A total of 69 patients with IBD aged 18 to 70 years (44.0 ± 1.4 years) were examined. All patients were divided into 2 groups depending on the nosology. 1st group consisted of 45 patients with UC, among them 23 women (51.1 %) and 22 men (48.9 %), 2nd group – 24 patients with HC, of which 14 women (58.3 %) and 10 men (41.7 %). To assess endothelial function, the method for determining endothelium-dependent vasodilation of the brachial artery (BA) in a test with reactive hyperemia was used to assess the change in BA diameter (dPA), a ATL PHILIPS HDI 5000 SONOS CT ultrasound machine with a 7.5 MHz linear transducer was used. The endothelial function index was calculated as the difference between dPA after decompression and the initial value, expressed as a percentage. The content of a soluble vascular cell adhesion molecule 1 (VCAM-1) was determined in blood serum by an enzyme immunoassay using a test system («Bender MedSystems GmbH», Austria) using an enzyme immunoassay analyzer «Stat Fax 303 Plus» («Awareness Technology Inc.», USA). The number of desquamated endothelial cells in the peripheral blood was determined by the method of J. Hladovec. Results. In the study of endothelium-dependent vasodilation (EDVD) PA in a test with reactive hyperemia, dysfunctions of the vascular endothelium were found in 75.4 % of the examined patients. Changes in vascular endothelial function were found in 82.3 % of patients with UC and 62.5 % with CC, mainly due to endothelial dysfunction (ED). Significant differences were found between the indicators of the average increase in dPA in the test with reactive hyperemia with decreased endothelial function (DEF) and normal endothelial function (NEF), as well as with DEF and ED in patients with severe UC. ED was observed 5.2 times more often than NEF (c2 = 56.8; p &lt; 0.001) and 2.6 times more often than PFE (c2 = 31.5; p &lt; 0.001). With moderate severity of the disease, DEF and ED occurred with the same frequency and 2.2 times higher than the number of patients with NEF (c2 = 11.3; p = 0.0008), changes in endothelium-dependent vasodilation were accompanied by a significant increase in the VCAM-1 level in serum of all IBD patients, but the highest expression of VCAM-1 was observed in UC. At the same time, the concentration of VCAM-1 was inversely correlated with endothelium-dependent vasodilation of BA (r = - 0.54, p &lt; 0.01), which is confirmed by the quantitative characteristics of the level of VCAM-1 in various states of the endothelium. The study of the content of circulating desquamated endothelial cells in the peripheral blood made it possible to establish an increase in their number by 5 times with ED – up to (15.5 ± 4.8) × 104/L (p &lt; 0.05), 2 times with DEF – up to (5.7 ± 0.3) × 104/L (p &lt; 0.001) versus (3.1 ± 0.4) × 104/L in the control group. An inverse correlation was found between the number of desquamated endothelial cells and endothelium-dependent BA vasodilation (r = - 0.59, p &lt; 0.01). Conclusions. The results of a comprehensive study of the functional state of the vascular endothelium indicate that the course of IBD is accompanied by a syndrome of endothelial dysfunction (with a predominance of DE), which is characterized by a decrease in endothelium-dependent vasodilation of BA, an increase in the level of VCAM-1 and the content of circulating desquamated endothelial cells in the blood. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, endothelial dysfunction.

Effects of Arm-cranking Training with Electrical Muscle Stimulation on Vessel Function.

This study aimed to determine whether arm-cranking training with electrical muscle stimulation (EMS) results in a greater improvement in vessel function than performing the same exercise without EMS. First, nine healthy young men performed two 20-min arm-cranking trials at 50% V˙O2max with and without EMS applied to the lower limbs. The flow-mediated vasodilation (FMD) of the right brachial artery was measured using a high-resolution ultrasound device. Both FMD and normalized FMD were increased significantly after the arm-cranking with EMS trial, and significant differences were observed between the two trials. Second, 16 healthy adult men were randomly assigned to either the arm-cranking exercise training (A) group or arm-cranking training with EMS (A+EMS) group. The subjects were engaged in 20 min of arm-cranking at 50% V˙O2max twice a week for 8 weeks with/without EMS applied to the lower limbs. The FMD increased significantly after A+EMS training session and the FMD in A+EMS group was significantly higher than that in the A group. These results indicate that acute/chronic endurance arm-cranking with EMS applied to the lower limbs improves the brachial artery endothelial function more markedly than the same exercise without EMS.