Endothelium-dependent Vasodilation In Patients Research Articles

#2887 ASSESSMENT OF EXTRA-BONE CALCIFICATION IN PATIENTS UNDERGOING PROGRAMMED HEMODIALYSIS

Abstract Background and Aims Chronic kidney disease is associated with the accumulation of so-called medium molecules in the blood, in particular parathyroid hormone, and the formation of secondary hyperparathyroidism with a tendency to extra-bone calcification. The most vulnerable organ in relation to calcification is the vascular wall. The ail of the study to study the features of vascular wall remodeling in patients with chronic kidney disease who are being treated with programmed hemodialysis. Method The study included 86 patients with CKD C5 (mean age 47.44±5.04 years) who had been on programmed hemodialysis for at least 6 months. All patients underwent examination, including multislice spiral computed tomography (MSCT) with an assessment of the calcium content in the coronary arteries (Agatston index), ultrasound examination of the carotid arteries with determination of the thickness of the intima-media complex, the degree of endothelium-dependent vasodilation in a sample with 5-minute compression of the brachial artery and determination of changes in the diameter of the brachial artery. The data obtained (presented in the form of an arithmetic mean and its standard error) were compared with normal values typical for a healthy population. Results There was an accumulation of calcium in the coronary vessels with an average Agatstone index of 146.83 ± 13.26 units. Also, during MSCT, calcifications were found in the aortic wall in 86 out of 57 patients. The intima-media complex in patients with CKD was significantly increased and averaged 1.21±0.06mm. The degree of endothelium-dependent vasodilation in patients with CKD was reduced and amounted to 5.48± 0.03% of the initial diameter of the brachial artery. Correlation analysis revealed significant positive associations of average strength between the value of the Agatson index, the thickness of the intima-media complex of the carotid arteries and the concentration of parathyroid hormone in peripheral blood (g = +0.58,P<0.05 with the Agatson index and P = 0.42, P<0.05 with the thickness of the intima-media complex), as well as a significant negative relationship between the product of the concentration of calcium and phosphorus in peripheral blood and the degree of endothelium-dependent vasodilation (g = -0.49, P<0.05). Conclusion In patients with CKD, against the background of programmed hemodialysis, there is a remodeling of the heart with an increase in the size of the heart cavities and LV myocardial mass, a violation of regional and general LV contractile function, LV diastolic dysfunction and an increase in pressure in the pulmonary artery system. The introduction of sevelamer hydrochloride into the therapy regimen is associated with the prevention of the progression of cardiac remodeling. Calcification of the aortic valve progresses, regardless of the therapy used. Vascular remodeling in patients with CKD on the background of programmed hemodialysis is manifested by an increase in the thickness of the intima-media complex of the carotid arteries and a violation of endothelium-dependent vasodilation in favor of paradoxical vasoconstriction. Against the background of calcium carbonate therapy, structural disorders of the vascular wall progress. The introduction of sevelamer phosphate binder into the therapy regimen allows to prevent the progression and improve the functional state of endothelial function.

Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019.

The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown. Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample. One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n = 34) and those recovered from mild symptoms of COVID-19 ( n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P = 0.001). In a sub-sample ( n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P = 0.006) with no significant difference between hospitalized ( n = 12) and nonhospitalized participants ( n = 10). In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

Нарушения эндотелий-зависимой вазодилатации у больных с микрососудистой стенокардией

Background: disorders of both endothelium-dependent and endothelium-independent vasodilation play a role in the pathogenesis of microvascular angina (MVA), the contribution of which may be different. Aim: to study the processes of endothelium-dependent vasodilation (EDV) in patients with primary MVA. Patients and Methods: an open prospective study included 60 patients (mean age 57.3±6.4 years) with MVA, confirmed clinical picture (chest pain), coronary angiography data (the absence of coronary artery stenosis), positive stress test (pain syndrome and/or ST segment depression by ≥2 mm by treadmill exercise stress test), positron emission tomography (PET) myocardial perfusion imaging (MPI) with tests (cold pressor test and with adenosine). Patients with diseases that can lead to secondary microvascular dysfunction were not included in the study. To evaluate the processes of EDV, all patients underwent the following evaluations: peripheral arterial tonometry (PAT), assessment of circulating endothelial cells (CEC), high-sensitivity C-reactive protein (hsCRP), endothelin-1 (ET-1), total antioxidant status. Adding that, the results of a cold pressor test during PET were analyzed. Results: the majority of the examined patients were women — 81.7%. Most of the female patients included in the study (93.9%) were postmenopausal. In all patients with MVA, according to the data of PET MPI with cold pressor test, signs of EDV disorder were detected as a decrease in coronary blood flow through the three coronary arteries. During PET, the index of reactive hyperemia was reduced (<1,67) in all examined patients and amounted to 1.43±0.15. According to the results of laboratory studies, there was an increase in the level of ET-1 and CEC — 3,335 [1,545; 3,952] fmol/L and 14±8 cells/3×105 leukocytes, respectively. The CRP level was 4,44 [1.02; 4.45] mg/L. The total antioxidant capacity was reduced in 53 (88%) patients, the average values of the indicator were 289,03±52,14 μmol/L. Conclusion: according to laboratory and instrumental studies, signs of endothelial dysfunction, namely disorders of EDV, were revealed in all examined patients with primary MVA. KEYWORDS: microvascular angina, peripheral arterial tonometry, endothelium-dependent vasodilation, positron emission tomography. FOR CITATION: Leonova I.A., Zakharova O.V., Boldueva S.A. Disorders of endothelium-dependent vasodilation in patients with microvascular angina. Russian Medical Inquiry. 2022;6(8):427–432 (in Russ.). DOI: 10.32364/2587-6821-2022-6-8-427-432.

Changes of endothelial function and intracardiac hemodynamics during implantation of different types of pacemakers

Aim. To determine the dynamics of endothelial function and intracardiac hemodynamics during implantation of different types of pacemakers. Material and methods. The study involved 61 patients, 29 of them were implanted with single-chamber pacemaker (the first group), 32 — two-chamber pacemaker (second group) with sick sinus syndrome (SSS), as well as patients with 2-3 degrees AV conduction disorder. Test with endothelium-dependent vasodilation of the brachial artery was performed using the standard technique and the velocity parameters of blood flow were determined. Parameters of intracardiac hemodynamics and left atrial (LA) function were determined. These studies were conducted in patients initially upon admission to the hospital and 2 months later implantation of pacemaker. Results. Endothelium-dependent vasodilation significantly deteriorated in patients with single-chamber pacemaker which initially was 6,1 [2,74;9,815]% and in 2 months decreased to 5,4 [2,37;7,55]% (p=0,05). There was a tendency to deterioration of left ventricular (LV) contractile function accompanied by a decrease in ejection fraction (EF) to 55,04 [49,04;68,72]%, and decrease emptying fraction of LA to 37,36 [31,67;52,85]%. There was a tendency to increase the volume index of LA which indicates an increasing overload of the volume and pressure of LA. There was a significant increase in the degree of endothelium-dependent vasodilation in patients of the second group initially compiling a 3,25 [2,15;6,61]% and then reaches 6,15 [2,75;8,97]% 2 months after surgery (p <0,04). There was no overload in the volume and pressure of LA and improved indirect signs of LV compliance parameters (growth of end-systolic dimension and volume) and decreased LV EF to 53,23 [44,1;69,95]%. In patients in the first group there was a tendency to increase peripheral resistance to 1227 [1065;1318] dyne x cm -5 x sec, accompanied by a significant decrease in blood flow rate. In the second group there was a tendency to reduce peripheral resistance to 1215 [1136;1391] dyne x cm -5 x sec and a significant increase in blood flow rate. There was a significant correlation between the systole LA dimension and total peripheral resistance in patients with VVI stimulation (r=0,78, p=0,0022), which indicates an increase in total peripheral resistance with a change in blood flow from LA to LV and a decrease in cardiac output. Conclusion. Endothelial function deteriorates with single-chamber stimulation and improves with two-chamber stimulation. These changes are based on shear stress and nitric oxide endothelium secretion the changes of which depend on the characteristics of central and peripheral hemodynamics.

Interrelation of Cardiovascular Diseases with Anaerobic Bacteria of Subgingival Biofilm.

Aims:The aim of this study is to study the colonization of subgingival biofilm (SGB) with periodontopathogenic bacteria species and endothelium-dependent vasodilation in patients with coronary heart disease and concomitant periodontitis.Subjects and Methods:Forty-five patients with cardiovascular diseases (CVDs) were examined – 28 women (62%) and 17 men (38%) aged 53–76 years, including 15 patients with acute myocardial infarction (AMI), 15 patients with exertional angina (pectoris), and 15 patients with chronic periodontitis (CP) without CVD. Dental and cardiological health conditions were determined, a biochemical blood test was conducted, endothelium-dependent vasodilation in the brachial artery was measured, and DNA of periodontopathogenic bacteria in SGB was detected.Results:A reliable interrelation between the colonization of SGB with periodontopathogenic bacteria and development of AMI was established. In AMI patients, the frequency of Porphyromonas gingivalis, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans detection was significantly higher than in the group of participants without cardiovascular disease. The presence of P. gingivalis and A. actinomycetemcomitans in patients with CP directly correlated with severity of periodontal tissue destruction. Endothelium-dependent vasodilation in the brachial artery moderately correlated with patient's cardiological condition (r = 0.3284), biochemical markers of atherosclerosis development (r = 0.6465), and frequency of P. intermedia detection in periodontal pockets (r = 0.3828).Conclusions:Periodontal status in patients with AMI is characterized by unsatisfactory and poor hygiene, increased indices of bleeding on probing, and periodontal pocket depth in comparison to groups of patients with angina pectoris and CP without cardiovascular pathology.

Skin Blood Flow and Vascular Endothelium Function in Uremia

Prevalence of dermatological disorder in patients with end-stage kidney disease is estimated as 50% to 100% in various studies. Some of the skin lesions are specific for the diseases causing chronic kidney disease (CKD), some are associated with CKD, and still others are the dermatological manifestation of uremia. Microangiopathy was also found in both arterioles and venule in the skin biopsy of "normal looking" skin in patients with end-stage kidney disease. In a cross-sectional study in patients on dialysis, we measured skin blood flow (SBF) using laser Doppler device in a standardized way at various areas of lower extremities at 2 different local skin temperatures: 35°C and 44°C. Local heating increases skin perfusion by mechanisms dependent on nitric oxide (NO). SBF was impaired in CKD patients Stage 5 on HD, particularly in those with diabetes mellitus as a cause of CKD. The reduced response in the SBF to the heat in our patients may be due to decreased generation of NO in uremia. Endothelium-dependent vasodilatation in patients on dialysis and the response of the skin microcirculation to acetylcholine was diminished in hypertensive patients on dialysis. Similarly, patients with diabetes mellitus had decreased SBF during intradermal microdialysis with a NO synthase inhibitor. Multiple uremic toxins have been studied invitro and show to cause various degree of endothelial cell dysfunction. Unfortunately, no clear benefit has been described in CKD patients to different intervention aimed to reduce uremic toxin effect on endothelium. There are no long-term data on the factors which can modify endothelium function in uremia, but non pharmacologic interventions, diet, and several pharmacologic approaches could be beneficial. Measurement of SBF can be useful in evaluation of vasculopathy in CKD population and can potentially be used for assessment of vascular response during specific clinical intervention.

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus.

Paricalcitol and endothelial function in chronic kidney disease trial.

Altered vitamin D metabolism and low levels of the active form of this vitamin, 1,25-dihydroxy-vitamin D, is a hallmark of chronic kidney disease (CKD), but there is still no randomized controlled trial testing the effect of active forms of vitamin D on vascular function in patients with CKD. Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY) is a double-blinded randomized controlled trial (ClinicalTrials.gov, NCT01680198) testing the effect of an active form of vitamin D, paricalcitol (2 μg/d×12 weeks) on endothelium-dependent and endothelium-independent vasodilatation in 88 patients with stage 3 to 4 CKD and parathormone >65 pg/mL (paricalcitol, n=44; placebo, n=44). Paricalcitol treatment reduced parathormone (-75 pg/mL; 95% confidence interval, -90 to -60), whereas parathormone showed a small rise during placebo (21 pg/mL; 95% confidence interval, 5-36). Blood pressure did not change in both study arms. Baseline flow-mediated dilation was identical in patients on paricalcitol (3.6±2.9%) and placebo (3.6±2.9%) groups. After 12 weeks of treatment, flow-mediated dilation rose in the paricalcitol but not in the placebo group, and the between-group difference in flow-mediated dilation changes (the primary end point, 1.8%; 95% confidence interval, 0.3-3.1%) was significant (P=0.016), and the mean proportional change in flow-mediated dilation was 61% higher in paricalcitol-treated patients than in placebo-treated patients. Such an effect was abolished 2 weeks after stopping the treatment. No effect of paricalcitol on endothelium-independent vasodilatation was registered. Paricalcitol improves endothelium-dependent vasodilatation in patients with stage 3 to 4 CKD. Findings in this study support the hypothesis that vitamin D may exert favorable effects on the cardiovascular system in patients with CKD.

Effect of L-arginine on endothelial dysfunction in patients with congenital mitral valve prolapse

АIM. To study the effect of L-arginine on endothelium-dependent vasodilatation in patients with congenital mitral valve prolapse and different degrees of regurgitation. Methods. The study included 86 patients [36 (41.9%) males and 50 (58.1%) females aged 15-25 (mean age 19.9±1.42) years] with signs of congenital mitral valve prolapse. The first group included 41 patients were L-arginine (Tivortin) as a prophylaxis medication. The second group included 45 patients who were not taking L-arginine. Subgroup A of each group included 20 and 22 patients with stage I of mitral regurgitation, accordingly; subgroup B of each group included 21 and 23 patients with stage II of mitral regurgitation, accordingly. Results. In patients of the first group with mitral valve prolapse and stages I and II of mitral regurgitation, distinct positive changes were observed after 6 months of treatment with L-arginine. Compared to baseline data, in patients of the first group with stage I of mitral regurgitation brachial artery diameter increased by 1,44 times (р 0.001), resistance index - by 1.5 times (р 0.001); in patients with stage II of mitral regurgitation the following parameters increased by 1.65 and 1.39 times (р 0.001 and р 0.01) accordingly. At the same time, parameters of NO-system also improved in patients of the first group with stages I and II of mitral regurgitation after 6 months of treatment: endothelial NO synthase activity increased by 1.18 and 1.29 times (р 0.05 and р 0.02) accordingly, NO level decreased by 1.17 and 1.18 times (р 0.05), inducible NO synthase activity - by 1.17 and 1.29 times (р 0.05 and р 0.02), and there was a reduction of peroxynitrite levels by 1.23 and 1.34 times (р 0.02 and р 0.01), endotheline-1 - by 1.07 and 1.26 times (р 0.05 and р 0.02), vascular endothelial growth factor - by 1.08 and 1.24 times (р 0.05 and р 0.01) accordingly. Conclusion. Recommended doses of L-arginine restores the stream-dependent vasodilation, activity of the NO-system and process of angiogenesis after 6 months of treatment.

Selective endothelin ETA and dual ETA/ETB receptor blockade improve endothelium-dependent vasodilatation in patients with type 2 diabetes and coronary artery disease

AimsEndothelin-1 contributes to endothelial dysfunction in patients with atherosclerosis and type 2 diabetes. In healthy arteries the ETA receptor mediates the main part of the vasoconstriction induced by endothelin-1 whilst the ETB receptor mediates vasodilatation. The ETB receptor expression is upregulated on vascular smooth muscle cells in atherosclerosis and may contribute to the increased vasoconstrictor tone and endothelial dysfunction observed in this condition. Due to these opposing effects of the ETB receptor it remains unclear whether ETB blockade together with ETA blockade may be detrimental or beneficial. The aim was therefore to compare the effects of selective ETA and dual ETA/ETB blockade on endothelial function in patients with type 2 diabetes and coronary artery disease. Main methodsForearm endothelium-dependent and endothelium-independent vasodilatation was assessed by venous occlusion plethysmography in 12 patients before and after selective ETA or dual ETA/ETB receptor blockade. Key findingsDual ETA/ETB receptor blockade increased baseline forearm blood flow by 30±14% (P<0.01) whereas selective ETA blockade did not (14±8%). Both selective ETA blockade and dual ETA/ETB blockade significantly improved endothelium-dependent vasodilatation. The improvement did not differ between the two treatments. There was also an increase in endothelium-independent vasodilatation with both treatments. Dual ETA/ETB blockade did not significantly increase microvascular flow but improved transcutaneous pO2. SignificanceBoth selective ETA and dual ETA/ETB improve endothelium-dependent vasodilatation in patients with type 2 diabetes and coronary artery disease. ETB blockade increases basal blood flow but does not additionally improve endothelium-dependent vasodilatation.

Does vitamin C or its combination with vitamin E improve radial artery endothelium-dependent vasodilatation in patients awaiting coronary artery bypass surgery? : cardiovascular topics

We evaluated the vasodilatory effects of two antioxidants, vitamins C (ascorbic acid) and E (α-tocopherol), on radial artery and endothelium-dependent responses in patients awaiting coronary artery bypass surgery. The study was performed in three groups. The first group took 2 g of vitamin C orally (n = 31, vitamin C group), the second group took 2 g of vitamin C with 600 mg of vitamin E orally (n = 31, vitamins C + E group), and the third group took no medication (n = 31, control group). After baseline measurements were taken of the radial artery lumen diameter, flow volume and lumen area in the non-dominant radial artery, occlusion was maintained for five minutes with a pressure cuff placed around the arm. The measurements were taken again at the time of deflating the cuff, and 60 seconds later. The measurements were repeated after medication in two of the groups and after placebo in the third group. We compared values of the vitamin C group with those of the vitamins C + E group, and found that the latter were higher than those of the vitamin C group but not statistically significant. In the control group, there was no statistical difference. Vitamin C or its combination with vitamin E significantly enhanced endothelium-dependent vasodilatation in the radial circulation of patients with coronary artery disease. Its combination with vitamin E was superior to vitamin C administration alone for endothelial enhancement but this difference was not statistically significant. We hypothesised that vitamin C or its combination with vitamin E may be used as antioxidants for arterial graft patency in patients undergoing coronary artery surgery.

The effect of aerobic training on endothelium-dependent vasodilatation in patients with coronary artery disease who were revascularized and young men

Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impaired endothelial function has been observed in patients with CAD and those with CAD risk factors. Studies have shown that exercise can enhance endothelial function. Methods: This experimental cross-sectional study was conducted on patients with CAD (3 months after CABG and PCI) and students of medical school in 2011. Endothelium dependent dilation of the brachial artery was determined by using high-resolution vascular ultrasonography through flow-mediated vasodilatation (FMD) after induction of ischemia, and the data were analyzed using SPSS, dependent t-test and ANCOVA. Findings: The findings showed that at baseline, FMD was reduced in revascularized patients, when compared with healthy young men, after 8 weeks, and exercise training significantly improved FMD in patients underwent training group [from 4.31 ± 1.45 (SD)% to 6.15 ± 0.773 (SD)%, p p ed unchanged, and even after aerobic training, it did not significantly modify the brachial artery diameter in these groups. Conclusion: Our study demonstrates that endothelial dysfunction persisting in CAD patients after revascularization and aerobic training can improve endothelial function in different vascular beds in CAD patients and healthy young men. This may contribute to the benefit of regular exercise in preventing and restricting cardiovascular disease.

The endothelin receptor antagonist bosentan improves peripheral endothelial function in patients with type 2 diabetes mellitus and microalbuminuria: a randomised trial

Endothelial dysfunction is important in the development of vascular complications in diabetes. Patients with type 2 diabetes have increased production of the vasoconstrictor and pro-inflammatory peptide, endothelin-1. Short-term intra-arterial administration of endothelin antagonists improves endothelium-dependent vasodilatation in patients with type 2 diabetes. We tested the hypothesis that oral administration of the dual endothelin receptor antagonist, bosentan, improves peripheral endothelial function in patients with type 2 diabetes and microalbuminuria. This placebo-controlled and double-blind study was performed on 46 patients with type 2 diabetes and microalbuminuria (urine albumin/creatinine ratio >3 mg/mmol) at a medical university department. Patients were randomised to bosentan, 125 mg two times per day (n = 28), or placebo (n = 28) for 4 weeks. The computer-generated randomisation code was kept in sealed envelopes. Patients and people doing examinations or assessing outcomes were blinded. The primary endpoint was change in microvascular endothelium-dependent vasodilatation, based on change in digital reactive hyperaemia index. The secondary endpoint was change in brachial artery flow-mediated vasodilatation. Reactive hyperaemia index increased from 1.73 ± 0.43 (mean ± SD) at baseline to 2.08 ± 0.59 at follow-up (p < 0.05) in the bosentan group (n = 22), but did not change in the placebo group (1.84 ± 0.49 to 1.87 ± 0.47; n = 24). The change in reactive hyperaemia index from baseline was greater in the bosentan group than in the placebo group (p < 0.05). Nitroglycerine-induced digital hyperaemia was not affected. Brachial artery flow-mediated vasodilatation and blood pressure did not change during treatment. Oral treatment of 4 weeks duration with the dual endothelin receptor antagonist, bosentan, improves peripheral endothelial function in patients with type 2 diabetes and microalbuminuria.

High-intensity aerobic training improves endothelium-dependent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus

BackgroundThe aim of this study is to compare the effect of physical exercise program on the endothelial function of patients with metabolic syndrome and type 2 diabetes mellitus. MethodsPatients were randomized for high intensity aerobic training (HI: 80% maximum heart rate, n=10), low intensity aerobic training (LI: 55% of maximum heart rate, n=10) and control (n=11). Before and after 6 weeks of training, subjects performed the maximal exercise test and a study of the endothelial function, through a high resolution ultrasound of the brachial artery, which was assessed after reactive hyperemia (endothelium dependent vasodilation) and nitrate administration (endothelium independent vasodilation). ResultsA total of 31 patients with metabolic syndrome and type 2 diabetes mellitus were studied, with mean age of 58±6 years, The percentage diameter difference of the vessel after hyperemia was significantly higher for the high intensity group (HI before 2.52±2.85% and after 31.81±12.21%; LI before 3.23±3.52% and after 20.61±7.76%; controls before 3.56±2.33% and after 2.43±2.14%; p<0.05). ConclusionsHigh intensity aerobic training improved the functional capability and endothelium dependent vasodilator response, but it does not improve the endothelium independent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus.

Vildagliptin Improves Endothelium-Dependent Vasodilatation in Type 2 Diabetes

OBJECTIVETo investigate whether the dipeptidyl peptidase-4 inhibitor vildagliptin improves endothelium-dependent vasodilatation in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSSixteen subjects with type 2 diabetes (age 59.8 ± 6.8 years, BMI 29.1 ± 4.8 kg/m2, HbA1c 6.97 ± 0.61) on oral blood glucose–lowering treatment were included. Participants received vildagliptin 50 mg b.i.d. or acarbose 100 mg t.i.d. for four consecutive weeks in a randomized, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses to intra-arterially administered acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator).RESULTSInfusion of acetylcholine induced a dose-dependent increase in forearm blood flow in the experimental arm, which was higher during vildagliptin (3.1 ± 0.7, 7.9 ± 1.1, and 12.6 ± 1.4 mL ⋅ dL−1 ⋅ min−1 in response to three increasing dosages of acetylcholine) than during acarbose (2.0 ± 0.7, 5.0 ± 1.2, and 11.7 ± 1.6 mL ⋅ dL−1 ⋅ min−1, respectively; P = 0.01 by two-way ANOVA). Treatment with vildagliptin did not significantly change the vascular responses to sodium nitroprusside.CONCLUSIONSFour weeks’ treatment with vildagliptin improves endothelium-dependent vasodilatation in subjects with type 2 diabetes. This observation might have favorable cardiovascular implications.

Estimation of the Vascular Endothelial Functions at Influence of Infrared Beams of a Narrow Spectrum

The purpose of the work was -to identify influence of narrow spectral infra-red (IR) irradiators on endothelium-dependent vasodilatation in patients with and without erectile dysfunction (ED). 78 males with ED were examined. 12 practically healthy males comprised a control group. All patients with ED divided two groups: 1-arteriogenic ED (n=61) and 2-non arteriogenic ED (n=17). All males passed complex examination (common medical and sexual story; IIEF, hormonal state, level of lipid and glucose). An endothelial function of the Arteria cavernosa profunda (ACP) was determined with an original technique with use of the sonography. Doppler sonography was used in the same patients examined following application of an IR irradiator. Percent of increase the diameter ACP (PID ACP) was calculated according to the formula. The mean values of PID ACP for control group have formed 62,2%; for 1ED group – 12,5% and 2ED group – 51,7%. A comparative analysis of mean values the PID ACP demonstrated that the indicator was statistically less in the group with ED in comparison with the control one and 2 group with ED. The analysis of the data obtained allowed us to suggest a 30% threshold value of the PID ACP for identification of an endothelial dysfunction at carrying out of the test with use of a narrow spectral IR irradiator. The method developed is informative in diagnostics of endothelial dysfunction of the penile artery and allow to delimit different of type ED. We think that it will take a relevant place in a comprehensive examination of patients with ED.

Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes

Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (HbA(₁c)) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30-300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. Patients were normotensive (systolic arterial pressure: 131.1±10.6 mmHg) and on good metabolic control (HbA(₁c): 6.6±0.6%). Microalbuminuric patients presented impaired venous (32.9±17.4 vs 59.3±26.5%; p=0.004) and arterial vasodilation (1.8±0.9 vs 5.1±2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=-0.62; p<0.001) and HbA(₁c) (r=-0.41; p=0.032). The same was observed between flow mediated arterial vasodilation and albuminuria (r=-0.49; p=0.007) and HbA(₁c) (r=-0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis.

Alpha‐lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo‐controlled randomized trial

The aim of this study was to investigate the effect of alpha-lipoic acid (ALA) treatment on endothelium-dependent and -independent vasodilatation, assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus. A total of 30 subjects with type 2 diabetes were included in this randomized, controlled, double-blinded, parallel group study. FBF responses to intra-arterial acetylcholine (ACh) and glycerol trinitrate (GTN) were measured before and after 21 days of intravenous treatment with 600 mg alpha-lipoic acid or placebo. FBF responses were comparable at baseline. After treatment, FBF reactivity to ACh and GTN was unchanged in subjects receiving placebo. By contrast, ALA treatment increased endothelium-dependent vasodilatation to ACh (P < 0.05) but not to GTN compared with baseline. Intravenous ALA treatment improves endothelium-dependent vasodilatation in patients with type 2 diabetes, in the absence of effects on forearm vasomotor function. If this salutary action translates into vascular risk reduction remains to be established.

Sarpogrelate Hydrochloride, a Selective 5-hydroxytryptamine2A Antagonist, Augments Autologous Bone Marrow Mononuclear Cell Implantation–induced Improvement in Endothelium-dependent Vasodilation in Patients With Critical Limb Ischemia

The purpose of this study was to determine the effect of a combination of bone marrow mononuclear cell (BM-MNC) implantation and sarpogrelate, a selective 5-HT(2A) antagonist, on endothelial function in patients with critical limb ischemia (CLI). We evaluated the leg blood flow (LBF) responses to acetylcholine (ACh) and sodium nitroprusside before and after BM-MNC implantation in 16 patients with CLI. We divided patients with CLI into 2 groups: those cotreated with sarpogrelate orally for 12 weeks (sarpogrelate group, n = 8) and those who remained on conventional therapy (control group, n = 8). LBF was measured by strain gauge plethysmography. BM-MNC implantation improved ankle brachial pressure index, transcutaneous oxygen pressure, and pain-free walking time. There was no significant difference in these parameters between the 2 groups. Before BM-MNC implantation, LBF responses to ACh were similar in the sarpogrelate group and control group. Twelve weeks of BM-MNC implantation enhanced LBF responses to ACh in the sarpogrelate and control groups. After 12 weeks of BM-MNC implantation, LBF response to ACh was significantly greater in the sarpogrelate group than in the control group. BM-MNC implantation did not alter the LBF responses to sodium nitroprusside in either group. These findings suggest that BM-MNC implantation improved not only limb ischemic symptoms but also endothelium-dependent vasodilation in patients with CLI. A combination of BM-MNC implantation and sarpogrelate had a more beneficial effect on vascular function in these patients.

Endothelium-dependent contractions and endothelial dysfunction in human hypertension.

The endothelium is a crucial regulator of vascular physiology, producing in healthy conditions several substances with a potent antiatherosclerotic properties. Accordingly, the presence of endothelial dysfunction is associated with subclinical atherosclerosis and with an increased future risk of cardiovascular events. A large body of evidence supports the fundamental role of nitric oxide (NO) as the main endothelium-derived relaxing factor. However, in the presence of pathological conditions, such as hypertension, endothelial cells, in response to a number of agents and physical stimuli, become also a source of endothelium-derived contracting factors (EDCFs), including endothelins and angiotensin II and particularly cyclooxygenase-derived prostanoids and superoxide anions. These latter were at first identified as responsible for impaired endothelium-dependent vasodilation in patients with essential hypertension. However, cyclooxygenase-dependent EDCFs production is characteristic of the aging process, and essential hypertension seems to only anticipate the phenomenon. It is worth noting that both in aging and hypertension EDCF production is associated with a parallel decrease in NO availability, suggesting that this substance could be oxygen free radicals themselves. Accordingly, in hypertension both indomethacin, a cyclooxygenase inhibitor, and vitamin C, an antioxidant, increase the vasodilation to acetylcholine by restoring NO availability. In conclusion, hypertension is characterized by a decline in endothelial function, associated with a progressive decrease in NO bioavailability and increase in the production of EDCF. The mechanisms that regulate the balance between NO and EDCF, and the processes transforming the endothelium from a protective organ to a source of vasoconstrictor, proaggregatory and promitogenic mediators remain to be determined.