Improvement In Endothelium-dependent Vasodilation Research Articles

Effectiveness of Sulfide Balneopeloidtherapy in Patients with Hypertension in Comorbid Combinations: Randomized Prospective Study

INTRODUCTION. In the treatment of cardiovascular diseases, the use of hydrogen sulfide, which is a universal gas transmitter and performs many physiological functions in the body, is of interest.
 AIM. To evaluate the effectiveness of sulfide balneopeloid therapy (SBPT), carried out at the Klyuchi resort (Perm region), in patients with arterial hypertension (AH), as well as their combinations with coronary heart disease (CHD), prediabetes and cerebrovascular disease (CVD) with chronic ischemia brain (CHM).
 MATERIALS AND METHODS. A comparative randomized prospective study was conducted at the Klyuchi resort (Perm region), which studied the effectiveness of SBPT in patients with hypertension in various comorbid combinations. General inclusion criteria were the presence of hypertension and age from 40 to 70 years.
 RESULTS. The results of a study of the effectiveness of different durations of SBPT in patients with hypertension showed that when a course of SBPT was carried out for 14 days, the hypotensive effect was less significant, while mid-term observation revealed that the hypotensive effect after a 21-day course of SBPT persisted for up to 6 months, and after 14-day course — 3 months. In patients with hypertension and prediabetes, complex therapy, including 14 days of SBPT, helps reduce the severity of clinical manifestations and improve quality of life; causes redistribution of fat deposits, improvement of blood pressure profile, aortic compliance, endothelial and neurogenic circuit of skin microcurrent regulation; reduces the serum concentration of vascular endothelial growth factor (VEGF), leptin, and also increases the serum concentration of transforming growth factor beta 1 (TGF-β1). When treating patients with hypertension and coronary artery disease using SBPT, an increase in the activity of the parasympathetic part of the nervous system, a lipid-correcting effect, improvement of endothelium-dependent vasodilation and exercise tolerance. The results of a study of patients with hypertension with CVD and MS showed that patients who received a course of SBRT had a significant improvement in cognitive functions.
 DISCUSSION. The effects that develop during SBPT are associated with the polymodal effect of the H2S molecule on the main metabolic signaling pathways and regulatory mechanisms of the body’s hormonal-humoral systems, which leads to optimal regulation of micro- and macrohemodynamics, favorable changes in lipid metabolism, trophological status and trophic factors.
 CONCLUSION. SBPT, carried out at the Klyuchi resort (Perm Region), is effective in patients with hypertension, including various comorbid combinations — hypertension and prediabetes, hypertension and ischemic heart disease, CCI.

Abstract 14157: Effects of Follistatin on the Regulation of Vascular Function by Perivascular Adipose Tissue in a Model of Essential Hypertension

Introduction: We previously showed that follistatin (FST), a potent activin inhibitor, lowers BP in the spontaneously hypertensive rat (SHR), a model of essential HTN. This was associated with improved vessel structure (reduced collagen) and function (reduced hypercontractility and improved endothelium-dependent relaxation). FST also reduced vascular oxidative stress (ROS). Perivascular adipose tissue (PVAT) is known to regulate vascular tone. FST induces browning and thus increased thermogenic activity of peripheral adipose tissue. Transition from white to brown adipose tissue is associated with decreased risk of CVD. Here, we assess FST effects on PVAT and its regulation of SHR vascular function. Methods: SHR were treated with FST from 12-20 weeks of age. Normotensive WKY rats served as controls. Mesenteric resistance arteries were isolated with or without intact PVAT. Vessel function was assessed using wire myography. In separate studies, white mesenteric and brown aortic PVAT, or peripheral fat depots, were isolated from WKY rats. These were introduced to WKY mesenteric vessels to study PVAT-isolated function. Results: Intact PVAT augmented constriction to KCl in SHR, but not WKY arteries, an effect prevented by FST. Improvement in endothelium-dependent vasodilation in FST-treated SHR was PVAT-dependent. SHR PVAT had increased adipocyte size and ROS (by DHE), both reversed by FST. Isolated PVAT from WKY incubated with pyocyanin (30’) to induce ROS augmented the KCl response, suggesting that FST inhibition of PVAT oxidative stress in HTN restores beneficial vascular effects. Incubation of WKY vessels with brown PVAT inhibited constriction to KCl more effectively than did white PVAT. Interestingly, peripheral white adipose (inguinal) did not have any anticontractile effect. Brown adipose (interscapular) effects were intermediate. Conclusions: Improvement in anticontractile effects of PVAT by FST in resistance vessels is associated with reduced PVAT oxidative stress. Brown PVAT is more effective than white PVAT in inhibiting vessel contraction, and unlike white PVAT, peripheral white adipose does not have anticontractile effects. Future work will assess effects of FST on PVAT browning, and whether browning itself can improve BP.

Delayed Cutaneous Microvascular Responses With Non-consecutive 3 Days of Remote Ischemic Preconditioning.

The optimal frequency and duration of remote ischemic preconditioning (RIPC) that augments microvascular function is unknown. A single bout of RIPC increases cutaneous endothelial function for ∼48 h, whereas 1 week of daily RIPC bouts improves more sustained endothelium-independent function. We hypothesized that 3 days of RIPC separated by rest days (3QOD RIPC) would result in sustained increases in both endothelium-dependent and endothelium-independent functions. Cutaneous microvascular function was assessed in 13 healthy young participants (aged 20.5 ± 3.9 years; 5 males, 8 females) before 3QOD and then 24, 48, and 72 h and a week after 3QOD. RIPC consisted of four repetitions of 5 min of blood flow occlusion separated by 5 min of reperfusion. Skin blood flow responses to local heating (Tloc = 42°C), acetylcholine (Ach), and sodium nitroprusside (SNP) were measured using laser speckle contrast imaging and expressed as cutaneous vascular conductance (CVC = PU⋅mmHg–1). Local heating-mediated vasodilation was increased 72 h after 3QOD and the increased responsivity persisted a week later (1.08 ± 0.24 vs. 1.34 ± 0.46, 1.21 ± 0.36 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. 72 h, a week after 3QOD; P = 0.054). Ach-induced cutaneous vasodilation increased a week after 3QOD (0.73 ± 0.41 vs. 0.95 ± 0.49 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. a week after 3QOD; P < 0.05). SNP-induced cutaneous vasodilation increased 24 h after 3QOD (0.47 ± 0.28 vs. 0.63 ± 0.35 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. 24 h; P < 0.05), but this change did not persist thereafter. Thus, 3QOD induced sustained improvement in endothelium-dependent vasodilation but was not sufficient to sustain increases in endothelium-independent vasodilation.

Tactics of managing a cardiac patient with comorbidity: promising opportunities for correction of endothelial dysfunction

Background. Arterial hypertension (AH) and heart diseases are the leading causes of morbidity, mortality and the number of visits to the doctor. Cardiac patients are characterized by the frequent polymorbidity. The cardiovascular continuum, which predicts the course of events from atherosclerosis to the final stages of cardiovascular diseases (CVD), includes the following pathogenetic links: oxidative stress, inflammation and endothelial dysfunction (ED).&#x0D; Objective. To describe the management of a cardiac patient with comorbidity and promising options for the ED correction.&#x0D; Materials and methods. Analysis of the literature on this issue.&#x0D; Results and discussion. The previous paradigm of CVD development involved damage to target organs due to hypertension. Instead, according to the current paradigm, CVD are the result of the vascular dysfunction. The recently proposed paradigm indicates that all CVD are based on ED. Nitric oxide (NO) is the main molecule necessary for the proper functioning of the endothelium. NO takes part in the relaxation of blood vessels and smooth muscles, regulates the synthesis and secretion of a number of hormones, controls platelet activity and the interaction of leukocytes with vascular walls, participates in antipathogenic reactions of the immune system. ED is known to be a predictor of complications and poorer survival in patients with coronary heart disease. Dysfunctional endothelium promotes vasoconstriction, oxidation, inflammation and thrombosis. To improve the condition of the endothelium, it is advisable to increase the NO content. The increase in NO content can be the result of angiotensin-converting enzyme inhibitors, calcium channel blockers, sartans, statins, estrogens, antioxidants, and aspirin intake, as well as exercise. L-arginine is the substrate for the NO formation in human body. Potential mechanisms of L-arginine effect in AH include improvement of endothelial function, increase of vascular NO synthesis, decrease of endothelin-1 and angiotensin II activity, modulation of renal hemodynamics and reduction of oxidative stress. L-arginine therapy (9 g per day for 4 weeks) reduced systolic blood pressure by 4 mm Hg and diastolic – by 2.6 mm Hg. L-arginine also has a beneficial effect on the metabolic profile via increasing insulin sensitivity. The use of L-arginine is well studied in patients with chronic heart failure (HF) with preserved ejection fraction. In this category of patients, such treatment leads to an increase in glomerular filtration rate, improvement of endothelium-dependent vasodilation, reduction of the functional class of HF. The ESPEN guidelines on parenteral nutrition state that the use of L-arginine has both NO-dependent and NO-independent effects. The latter include the synthesis of creatine, proline and polyamines; stimulation of insulin and growth hormone secretion. Administration of L-arginine in combination with L-carnitine helps to eliminate the advanced glycation end products and to increase the rate of glomerular filtration.&#x0D; Conclusions. 1. The cardiovascular continuum includes such elements as oxidative stress, inflammation and endothelial dysfunction. 2. NO is the main molecule necessary for the proper functioning of the endothelium. 3. L-arginine is the substrate for the NO formation in human body. L-arginine also helps to improve endothelial function, to reduce the activity of endothelin-1 and angiotensin II, to modulate renal hemodynamics and to reduce oxidative stress. 4. L-arginine also has a beneficial effect on the metabolic profile via increasing insulin sensitivity. 5. In patients with chronic HF with preserved ejection fraction, treatment with L-arginine leads to an increase in glomerular filtration rate, improvement of endothelium-dependent vasodilation, reduction of the functional class of HF.

Pharmacology of treatment of vascular diseases with the help of endothelioprotectors

Background. Endothelioprotectors (EP) are a group of drugs with different pathogenetic mechanisms of action that prevent disruption and/or restore the structural and functional properties of vascular endothelium. EP are mainly used in the treatment and prevention of cardiovascular and cerebrovascular diseases and their complications.&#x0D; Objective. To describe the role of EP in modern therapy of vascular diseases on the example of L-arginine (Tivortin, “Yuria-Pharm”).&#x0D; Materials and methods. Analysis of literature data on this topic.&#x0D; Results and discussion. The endothelium can be considered as a separate organ that regulates the work of blood vessels. Nitric oxide (NO) is the main signaling molecule of the endothelium. In humans, NO is produced from L-arginine. The latter is a conditionally essential amino acid, which means that it is synthesized in sufficient quantities only in perfectly healthy adults. Arginine is practically not synthesized in children under 5 years of age and in persons over 50 years of age. The main food sources of arginine are meat (pork, poultry), chocolate, soybeans, however, nutrition may not always provide the necessary need for L-arginine. The effects of NO include decreased intracellular calcium, smooth muscle cell relaxation, and vasodilation. As a result, the total peripheral vascular resistance and blood pressure decrease. One of the leading negative factors affecting the heart and blood vessels is hypercholesterolemia, which disrupts the production and release of NO. An improvement in endothelium-dependent vasodilation and a reduction in the size of atherosclerotic plaques with L-arginine have been demonstrated in a rabbit model with hypercholesterolemia. Endothelial dysfunction is an important concept in modern cardiology and medical science. Its main manifestation is a decrease in the NO bioavailability, so in order to eliminate endothelial dysfunction, EP are prescribed. The ideal EP should have such properties as a pronounced cardio- and cerebroprotective effect, rapid onset of action, no side effects, and low cost. L-arginine (Tivortin) is one of the best known EP. It can be used in the treatment of chronic heart failure to increase exercise tolerance. Tivortin supplies the depleted endothelium with a substrate for NO synthesis, facilitating cell function. Tivortin can be used not only in cardiological patients. The research of V.V. Bezugla et al. (2017) showed that Tivortin aspartate for oral administration improves the general and special performance of athletes in cyclic and strength sports, as well as reduces the severity of psychophysiological stress. In addition, the neuro-rehabilitation properties of Tivortin are demonstrated, which justifies its feasibility in the treatment and prevention of stroke. In the study of M.M. Sunychuk et al. (2014) the inclusion of Tivortin (100 ml infusion once a day from the 4th day after stroke for 10-14 days) in the complex therapy contributed to a more positive dynamics of assessments on the NIHSS, Bartel and Rankin scales than the use of standard therapy only. Improvement of the cerebral blood flow with the use of Tivortin is shown in other scientific papers (Mankovsky B.N. et al., 2014). The beneficial effect of L-arginine on the course of hypertension has also been proven (West S.G. et al., 2005). Studies conducted at the Department of Pharmacology and Clinical Pharmacology of the Dnipropetrovsk Medical Academy confirmed the cardiotropic and vasotropic properties of L-arginine.&#x0D; Conclusions. 1. NO – the main signaling molecule of the endothelium – is produced from L-arginine, the production of which almost stops after 50 y. o. 2. EP supply the endothelium with a substrate for NO synthesis, facilitating its function. 3. L-arginine (Tivortin, “Yuria-Pharm”) improves clinical, laboratory and functional parameters in patients with cardiovascular and cerebrovascular diseases.

Abstract P095: Aerobic Exercise Training Reduces Endothelin-1-mediated Vasoconstriction In Postmenopausal Women

Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in postmenopausal women (PMW), contributing to their increased cardiovascular risk. Although aerobic exercise is beneficial in reducing ET-1 system activity in men, it is unknown whether this favorable vascular effect is conferred in women. In fact, contrary to men, it is uncertain whether aerobic exercise training improves endothelial dysfunction in PMW. We tested the hypothesis that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. We further hypothesized reductions in ET-1 vasoconstrictor tone underly exercise-induced improvements in endothelium-dependent vasodilatation in PMW. Methods: Forearm blood flow (FBF) responses to intra-arterial infusion of selective ET A receptor blockade (BQ-123, 100 nmol/min for 60 min), acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) in the absence and presence of ET A receptor blockade and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) were determined before and after a 12-week aerobic exercise training intervention in 20 healthy, sedentary PMW (56 + 1 yr). Results: All 20 PMW completed the exercise intervention, walking an average of 4.9 + 0.1 d/wk for 50 + 2 min/d at 71 + 1% of maximal heart rate. After the exercise intervention, BQ-123 elicited no significant change in resting FBF in the previously sedentary PMW compared with significant vasodilation (~25%) before exercise. FBF responses to acetylcholine were markedly higher (~25%; P&lt;0.05) after (from 4.3 + 0.3 to 13.8 + 0.8 mL/100 ml tissue/min) vs before (from 4.1 + 0.2 to 11.3 + 0.8 mL/100 ml tissue/min) exercise training. Moreover, before exercise training the co-infusion of BQ-123 with acetylcholine enhanced (~25%; P&lt;0.05) the vasodilator response (from 4.3 + 0.3 to 13.7 + 0.7 mL/100 mL tissue/min) compared with acetylcholine alone; after exercise training, the presence of BQ-123 did not significantly affect the vasodilator response to acetylcholine. Conclusions: These data demonstrate that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. Furthermore, decreased ET-1-mediated vasoconstriction is an important mechanism underlying aerobic exercise-induced improvement in endothelium-dependent vasodilation in PMW.

Особливості лікування хворих з артеріальною гіпертензією із супутнім ожирінням: невідоме про відоме

Introduction. Arterial Hypertension is the most common disease of the circulatory system. Today we can talk about it as a non-infectious epidemic. Obesity is a risk factor and a frequent comorbid condition in hypertension. The aim. Given the role of dopamine metabolism as one of the pathogenetic triggers of hypertension and obesity, to study the effect of a dopamine receptor agonist bromocriptine in this category of patients. Materials and methods. We examined 111 hypertensive patients with concomitant obesity and 18 hypertensive patients without obesity with dopamine (DA) metabolism disorders. 24 patients with concomitant obesity received the dopamine receptor agonist bromocriptine and the calcium antagonist amlodipine to correct their DA metabolism disorders. The level of DA was determined according to the daily excretion of DA in the urine by fluorometric method. Determination of angiotensin II (ATII) was performed using enzyme-linked immunosorbent assay. The concentration of lipids was determined using the enzymatic colorimetric method, blood pressure was assessed using Daily Monitoring of Blood Pressure (ABPM), the condition of the endothelium was determined using D.S Celermajer’s endothelium-dependent vasodilation assessment. Results. Concomitant obesity leads to a deeper impairment in the dopaminergic system, RAAS, lipid spectrum and endothelial status. Bromocriptine and amlodipine treatment resulted in a significant increase in urinary DA excretion by 1.77 times (77.4%) and a trend towards blood ATII increase, which confirms the assumption of similar mechanism of action of dopamine agonists and angiotensin II receptor antagonist; positivization of lipid spectrum parameters: significant reduction of total cholesterol by 5.7%, TG by 14.01%, LDL by 5.5%. Regarding other lipid metabolism, such as HDL, there was a trend towards increase by 4.6%, combined with a significant improvement in endothelium-dependent vasodilation by 54.8%, lower blood pressure and a positive modulating effect of the combination of these drugs on the daily blood pressure profile against the background of a significant decrease in body weight by 8.8%.

Arginase Inhibition Improves Endothelial Function in an Age-Dependent Manner in Healthy Elderly Humans.

Reduced bioavailability of nitric oxide (NO) is accompanied by endothelial dysfunction, which precedes clinical signs of atherosclerosis. The metalloenzyme arginase reciprocally inhibits the formation of NO and available data demonstrate that arginase contributes to reduced bioavailability of NO and increases the formation of reactive oxygen species. Emerging evidence suggests that arginase thereby plays a key role in the pathophysiology of age-associated vascular complications in animal models. However, the role of arginase in elderly human subjects in vivo with regard to macrovascular endothelial function is unclear. We hypothesized that arginase inhibition improves endothelial function in an age-dependent manner in elderly healthy subjects. Twenty-one subjects ranging from 48 to 75 years of age were included for evaluation of endothelial function using forearm venous occlusion plethysmography. Endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIDV) were evaluated before and after 2-hour intra-arterial infusion of the arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA). Baseline EDV, but not EIDV, was inversely correlated with age (p < 0.05, R = -0.48 and p = 0.62, R = -0.14, respectively). The magnitude of the improvement in EDV induced by arginase inhibition was significantly correlated with age (p < 0.05, R = 0.56), whereas EIDV was not (p = 0.25, R = 0.26). Arginase inhibition improves endothelial function in an age-dependent manner in elderly healthy subjects. The results suggest that arginase is a key factor contributing to endothelial dysfunction and may serve as a future pharmacological target for improving endothelial function in elderly subjects.

Regular aerobic exercise reduces endothelin-1-mediated vasoconstrictor tone in overweight and obese adults.

What is the central question of this study? Does aerobic exercise training reduce endothelin-1 (ET-1)-mediated vasoconstrictor tone in overweight/obese adults? And, if so, does lower ET-1 vasoconstriction underlie the exercise-related enhancement in endothelium-dependent vasodilatation in overweight/obese adults? What is the main finding and its importance? Regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight/obese adults, independent of weight loss. Decreased ET-1 vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults. Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in overweight and obese adults, contributing to vasomotor dysfunction and increased cardiovascular disease risk. Although the effects of habitual aerobic exercise on endothelium-dependent vasodilatation in overweight/obese adults have been studied, little is known regarding ET-1-mediated vasoconstriction. Accordingly, the aims of the present study were to determine the following: (i) whether regular aerobic exercise training reduces ET-1-mediated vasoconstrictor tone in overweight and obese adults; and, if so, (ii) whether the reduction in ET-1-mediated vasoconstriction contributes to exercise-induced improvement in endothelium-dependent vasodilatation in this population. Forearm blood flow (FBF) in response to intra-arterial infusion of selective ETA receptor blockade (BQ-123, 100nmolmin-1 for 60min), acetylcholine [4.0, 8.0 and 16.0μg(100mltissue)-1 min-1 ] in the absence and presence of ETA receptor blockade and sodium nitroprusside [1.0, 2.0 and 4.0μg(100mltissue)-1 min-1 ] were determined before and after a 3month aerobic exercise training intervention in 25 (16 men and nine women) overweight/obese (body mass index 30.1±0.5kgm-2 ) adults. The vasodilator response to BQ-123 was significantly lower (∼25%) and the FBF responses to acetylcholine were ∼35% higher after exercise training. Before the exercise intervention, the co-infusion of acetylcholine plus BQ-123 resulted in a greater vasodilator response than acetylcholine alone; however, after the exercise intervention the FBF response to acetylcholine was not significantly increased by ETA receptor blockade. These results demonstrate that regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight and obese adults. Moreover, decreased ET-1-mediated vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults.

Effects of a novel ACE inhibitor, 3-(3-thienyl)-l-alanyl-ornithyl-proline, on endothelial vasodilation and hepatotoxicity in l-NAME-induced hypertensive rats.

Nitric oxide (NO) is a widespread biological mediator involved in many physiological and pathological processes, eg, in the regulation of vascular tone and hypertension. Chronic inhibition of NO synthase by NG-nitro-l-arginine methyl ester (l-NAME) hydrochloride results in the development of hypertension accompanied by an increase in vascular responsiveness to adrenergic stimuli. Recently, we developed a novel sulfur-containing angiotensin-converting enzyme inhibitor: 3-(3-thienyl)-l-alanyl-ornithyl-proline (TOP). Our previous studies indicated a superior nature of the molecule as an antihypertensive agent in spontaneously hypertensive rats (showing the involvement of renin–angiotensin–aldosterone system) in comparison to captopril. The aim of the present study was to investigate the effect of TOP on NO pathway in l-NAME-induced hypertensive rats, and captopril was included as the standard treatment group. Treatment with both TOP (20 mg/kg) and captopril (40 mg/kg) prevented the development of hypertension in l-NAME model, but TOP showed better restoration of NO and normal levels of angiotensin-converting enzyme. In addition, in vitro vasorelaxation assay showed an improvement in endothelium-dependent vasodilation in both the cases. Further, the biochemical (malondialdehyde, alanine aminotransferase, and aspartate aminotransferase) and the histopathological effects of TOP on rat liver tissues revealed a protective nature of TOP in comparison to captopril in the l-NAME model. In conclusion, TOP at 50% lesser dose than captopril was found to be better in the l-NAME model.

Study of endothelial function response to exercise training in hypertensive individuals (SEFRET): study protocol for a randomized controlled trial.

BackgroundEndothelial dysfunction is a hallmark of diabetes mellitus and systemic arterial hypertension (SAH) and an early maker for atherosclerosis. Aerobic exercise training is known to enhance endothelial function, but little is understood about the effects of resistance or combined exercise training on endothelial function. The aim of this study is to investigate the effect of a 12-week aerobic (AT), resistance (RT), or combined (aerobic and resistance, CT) training program on endothelial function and assess associated effects on blood pressure in individuals with SAH.Methods/designEighty-one subjects with SAH aged 18 to 70 years will be selected and randomly assigned to three types of exercise training: AT, RT or CT. The study will involve the following procedures and tests: anamnesis, anthropometric assessment, echocardiography, blood pressure measurements through ambulatory blood pressure monitoring, flow-mediated dilation, ergospirometry, one repetition maximum test (1-RM), and blood collection (number of circulating endothelial progenitor cells, number of circulating endothelial microparticles, lipid profile, glucose, glycated hemoglobin, and creatinine). The AT intervention will consist of a 40-min exercise session with progressive intensities ranging from 50 to 75 % of heart rate reserve. The RT intervention will consist of a 40-minute session with four sets of six to 12 repetitions with a rest period of 60 to 90 seconds between each set and each type of exercise. Weight loads will be adjusted to 60 to 80 % of 1-RM for six types of exercise. The CT intervention will consist of a 20-min aerobic exercise session, followed by an additional 20-min resistance exercise session; each resistance exercise will have two sets less to match the total training volume.DiscussionThe study results are expected evidence of cardiovascular protective effects of different types of exercise training through the modulation of endothelial function in hypertensive individuals. Knowing the magnitude of improvement of endothelium-dependent vasodilation for the different types of exercise training can provide scientific evidence for the prescription of exercise programs for vascular protection targeting hypertensive individuals.Trial registrationThe Brazilian Clinical Trials Registry (http://www.ensaiosclinicos.gov.br/) under RBR-9ygmdn and dated 1 March 2015.

CORRECTION OF VASCULAR DISTURBANCES IN PATIENTS WITH CHRONIC OBSTRUCIVE PULMONARY DISEASE IN COMBINATION WITH THE HYPERTONIC DISEASE: NEW DIRECTIONS OF PATHOGENETIC THERAPY

The purpose of the study was to study of effects of sulodexide on clinical and functional parameters in patients with chronic obstructive pulmonary disease (COPD) in combination with hypertension. 40 COPD patients were examined. Patients were divided into two groups of 20 people. One group received only basic COPD therapy and antihypertensive treatment, the other group - basic and antihypertensive therapy in combination with sulodexide. After a year of observation the assessment of the clinical course of the disease, and ventilatory lung function, cardiopulmonary hemodynamics, endothelium-dependent vasomotor function was done. In patients, additionally treated with sulodexide, the following parameters were marked: stabilization of blood pressure parameters, reduction of dizziness and headaches, increase of tolerance to physical load, reducing the number of exacerbations, improvement in spirometry, lung diffusion capacity, improvement of pulmonary hemodynamics parameters and improvement of endothelium-dependent vasodilation. Thus, the positive effect of sulodexide on clinical and functional parameters indicates the feasibility of further study of the use of angioprotectors in complex pathogenetic therapy of COPD.

Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia irrespective of their cholesterol levels.

Elevated LDL cholesterol is an important risk factor for atherosclerosis. Endothelial dysfunction, an early event in the development of atherosclerosis, is characterized by a reduction in nitric oxide (NO) bioavailability. Arginase has emerged as a key regulator of endothelial function through competition with NO synthase for the common substrate l-arginine. Arginase in endothelial cells is activated by oxidized LDL. The study aim was to investigate the importance of arginase for endothelial dysfunction in patients with familial hypercholesterolaemia (FH). Endothelial function was evaluated in 12 patients with heterozygous FH and 12 age-matched healthy normocholesterolaemic subjects using forearm venous occlusion plethysmography. The evaluations in FH patients occurred when they were on lipid-lowering therapy and 4 weeks after withdrawal of treatment. Endothelium-dependent vasodilatation (EDV) was assessed by intrabrachial artery infusion of serotonin, and endothelium-independent dilatation was assessed by infusion of nitroprusside before and after 120 min administration of the arginase inhibitor N (ω) -hydroxy-nor-l-arginine (nor-NOHA; 0.1 mg min(-1)). In FH patients LDL cholesterol increased from 4.3 ± 0.9 mmol L(-1) at baseline to 7.6 ± 1.9 mmol L(-1) at follow-up (P < 0.001). Arginase inhibition enhanced EDV in FH patients by a similar degree independent of lipid-lowering therapy. The improvement in EDV by arginase inhibition was significantly greater in FH patients than in the control group. Arginase inhibition results in greater improvement in endothelial function in patients with FH compared to healthy controls irrespective of their cholesterol levels. Arginase may be a promising therapeutic target for improving endothelial function in patients with hypercholesterolaemia.

Abstract 230: Protein Farnesylation Inhibitor Tipifarnib Prevents Development of Chronic Hypoxia-induced Pulmonary Hypertension

Study objectives: Small GTPase RhoB contributes to pulmonary vascular remodelling in pulmonary hypertension. Farnesylation of RhoB augments cell proliferation while geranylgeranylation of RhoB is believed to be pro-apoptotic. We hypothesized that farnesyltransferase inhibitors may prevent vascular pathology in pulmonary hypertension. We studied the effects of farnesyltransferase inhibitor Tipifarnib on pulmonary vascular remodelling and vasoreactivity in chronically hypoxic pulmonary hypertensive mice and cultured human pulmonary artery endothelial cells (HPAECs). Chemical proteomics was used to characterise Tipifarnib-induced changes in protein prenylation while label- free quantitative proteomics was used to characterise changes induced by overexpression of RhoB prenylation mutants: farnesylated-only or geranlygeranylated-only RhoB in HPAECs. The effects of Tipifarnib on Ras and Rho GTPases expression and activity, filamentous and globular actin levels and eNOS pathway, were also studied. Results: Oral administration of Tipifarnib significantly attenuated chronic hypoxia-induced pulmonary hypertension in mice. This protective effect was associated with a marked improvement of endothelium-dependent vasodilatation, reduction in pulmonary vascular muscularization and a decrease in the right ventricular systolic pressure. Tipifarnib reduced farnesylation and increased geranyl-geranylation of several proteins, including Rho GTPases and Ras and reduced their activity in vitro and in vivo. Tipifarnib-induced changes in cultured cells were associated with a decrease in cell proliferation, decreased polymerization of actin and increased eNOS mRNA and protein levels. Proteomic analysis of HPAECs overexpressing prenylation mutants of RhoB suggests that protective effects of Tipifarnib may result, at least in part, from inhibition of RhoB farnesylation. Conclusions: We demonstrate protective effects of farnesyltransferase inhibitor Tipifarnib in chronic hypoxia-induced pulmonary hypertension. The effects of Tipifarnib may result from inhibition of small GTPases activity and increase in NO signalling.

107 Effect of a Polyphenol-rich Diet on Vascular Function and other Markers of Cardiovascular Risk

IntroductionObservational evidence indicates that polyphenol-rich foods, in particular berries and dark chocolate, have the potential to influence cardiovascular disease (CVD) risk.There are few polyphenol dietary intervention studies of sufficiently robust...

Mediterranean diet- and exercise-induced improvement in age-dependent vascular activity

The aging effect on microvascular integrity, marked by endothelial dysfunction and reduction in exercise tolerance, is a major cause of CVD (cardiovascular disease). Improved dietary habits, known to reduce morbidity and mortality, are also known to attenuate those aging effects. The present study investigated the effects of combined MD (Mediterranean diet) and exercise intervention on lower- and upper-limb cutaneous microvascular functions in an older healthy population. A total of 22 sedentary healthy participants (age, 55±4 years) underwent cardiopulmonary exercise tolerance test, and were assessed for their upper- and lower-limb vascular endothelial CVC (cutaneous vascular conductance) using LDF (laser Doppler fluximetry) with endothelium-dependent [ACh (acetylcholine chloride)] and -independent [SNP (sodium nitroprusside)] vasodilation. Participants were then randomized into two groups: MD and non-MD, and followed an 8-week intervention programme, which included discontinuous treadmill running based on each individual's exertion, twice per week. Exercise training improved CVC in both groups (e.g. 0.42±0.19 compared with 1.50±1.05 and 0.47±0.26 compared with 1.15±0.59 at 1000 μCb for MD and non-MD respectively; P<0.001). This was also combined by improvement in the exercise tolerance indicated by increased VT (ventilatory threshold) in both groups [12.2±2.8 compared with 14.8±2.8 ml·(kg of body weight)(-1)·min(-1) and 11.7±2.7 compared with 14.6±3.2 ml·(kg of body weight)(-1)·min(-1) for MD and non-MD groups respectively; P<0.05]. However, the MD group showed greater improvement in endothelium-dependent vasodilation than non-MD [ANCOVA (analyses of co-variance), P=0.02]. The results of the present study suggest that compliance with MD, combined with regular moderate exercise, improves age-provoked microcirculatory endothelial dysfunction and increases exercise tolerance, both responsible for reducing cardiovascular risk in this age group.

Scientific Opinion on the substantiation of health claims related to monomeric flavan-3-ols from apples and improvement of endothelium-dependent vasodilation (ID 1936) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

Scientific Opinion on the substantiation of health claims related to monomeric flavan-3-ols from apples and improvement of endothelium-dependent vasodilation (ID 1936) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

Scientific Opinion on the substantiation of health claims related to walnuts and maintenance of normal blood LDL-cholesterol concentrations (ID 1156, 1158) and improvement of endothelium-dependent vasodilation (ID 1155, 1157) pursuant to Article 13(1) of

Scientific Opinion on the substantiation of health claims related to walnuts and maintenance of normal blood LDL-cholesterol concentrations (ID 1156, 1158) and improvement of endothelium-dependent vasodilation (ID 1155, 1157) pursuant to Article 13(1) of

Scientific Opinion on the substantiation of health claims related to Camellia sinensis (L.) Kuntze (tea), including catechins in green tea, and improvement of endothelium-dependent vasodilation (ID 1106, 1310), maintenance of normal blood pressure (ID 131

Scientific Opinion on the substantiation of health claims related to Camellia sinensis (L.) Kuntze (tea), including catechins in green tea, and improvement of endothelium-dependent vasodilation (ID 1106, 1310), maintenance of normal blood pressure (ID 131

Scientific Opinion on the substantiation of health claims related to rutin and improvement of endothelium-dependent vasodilation (ID 1649, 1783) and protection of DNA, proteins and lipids from oxidative damage (ID 1784) pursuant to Article 13(1) of Regula

Scientific Opinion on the substantiation of health claims related to rutin and improvement of endothelium-dependent vasodilation (ID 1649, 1783) and protection of DNA, proteins and lipids from oxidative damage (ID 1784) pursuant to Article 13(1) of Regula