Improvement In Vascular Function Research Articles

Statin Therapy Does Not Significantly Alter Microvascular Function in Uncomplicated Hypertension

Objective Young patients with uncomplicated hypertension are frequently exempt from statin therapy as they generally fall below current treatment thresholds. This study examined whether there may be evidence of improved microvascular function in young patients with grade 1 hypertension after 12 weeks of statin therapy. Methods This was a randomized double-blind placebo-controlled crossover study in which 42 statin-naïve participants with grade 1 hypertension (mean systolic/diastolic blood pressure 142/92 mmHg) were randomized to receive either simvastatin 40 mg or a placebo for 12 weeks, followed by a 4-week washout period, after which the arms crossed for a further 12 weeks. Measures of vascular function were recorded at the beginning and end of each study period equating to four measures in total. The brachial artery was studied by flow-mediated dilatation (FMD) together with the resistive and pulsatility indices and mean velocity of flow. Results Statin therapy did not significantly alter the change in FMD seen in the brachial artery [standardized differential mean = 0.02 (0.23), confidence interval (CI) = −0.45 to 0.48, p = 0.932]. No significant changes were seen in the brachial artery mean velocity (CI = −9.68 to 11.51, p = 0.861), resistive index (CI = −0.11 to 0.12, p = 0.903), or pulsatility index (CI = −5.82 to 4.91, p = 0.864). Conclusion This study did not demonstrate any significant changes in established measures of microvascular function after treatment with a statin in a young hypertensive population with no antecedent cardiovascular disease. This may indicate that either the intervention was insufficiently vasoactive to produce a clinically detectable improvement in vascular function, or that the means used to assess the microvasculature were insufficiently sensitive to detect what may have been quite minor changes.

Acute Exercise-induced Angiogenic T Cell Redistribution Is Attenuated In Older Men

Circulating CD31+ T cells (TANG) possess significant pro-angiogenic capabilities, contribute to maintenance of endothelial function, and are reduced in those with vascular-related diseases. Therefore, maintaining high levels of these cells may be important for vascular health benefits. Acute bouts of exercise stimulate an increase in circulating T-cells, including TANG cells. Ageing is associated with a chronic reduction in TANG cells. PURPOSE: To determine the influence of age on the exercise-induced increases in circulating TANG cells. METHODS: Eight young (18-25yrs) and eight older (60-75yrs) men underwent a 30-minute cycling bout at 75% of their pre-determined maximum oxygen uptake (VO2max). Peripheral blood samples were taken pre-, immediately post-, and 1 hour post-exercise. Blood samples were used to quantify circulating TANG cells by flow cytometry. TANG were defined as peripheral blood mononuclear cells expressing CD3 and CD31. In addition, these cells were further characterised using antibodies against CD4 and CD8. Mixed model repeated measures analyses of variance (ANOVA) were performed to examine the effect of age, time and interactions of such (age x time) on changes in circulating TANG cells. RESULTS: Acute exercise stimulated an increase in circulating TANG cells in both groups, with a significant time x age interaction found for total TANG cells (p=0.049), with older age group displaying reduced circulating cell response to the exercise bout (95.62±7.71% vs. 78.09±7.25%, young vs. older individuals respectively). CD4+ TANG cells were also significantly affected by acute exercise, including a time x age interaction (p=0.0014, 107.09±10.56% vs. 79.88±10.04% increase). Despite CD8+ TANG cells significantly increasing in response to exercise (time, p=0.002, 71.44±7.30% pooled increase), no such effect of age was apparent (age x time, p=0.384). CONCLUSIONS: Exercise significantly increases the number of circulating TANG cells, however ageing attenuates the increase in total TANG and CD4+ TANG cells, but not CD8+ TANG subsets. Acute increases in circulating TANG cells may contribute to the improvements in vascular function observed with exercise, yet strategies to augment the TANG cell increase to exercise in older individuals may be required to promote vascular benefits of exercise.

Tadalafil for male lower urinary tract symptoms improves endothelial function.

To investigate the effects of tadalafil on vascular endothelial function and cardiovascular risk in patients with prostatic hyperplasia. Tadalafil 5 mg was given to 20 patients with prostatic hyperplasia for whom an α1-blocker was ineffective. Voiding symptoms and vascular endothelial function were investigated before and after 4 and 12 weeks of administration, using commercial tests for vascular function and vascular endothelial function. The participants had a median age of 65 years, a mean body mass index of 24.2 and a mean prostate volume of 36.2 mL measured using transabdominal sonography. Voiding symptoms were significantly improved by tadalafil, based on the International Prostate Symptom Score, quality of life index and overactive bladder symptom score (P < 0.05). There were also significant improvements in vascular function (change of brachial-ankle pulse wave velocity from 1701 [before] to 1657 [4 weeks tadalafil] and 1525 [10 weeks tadalafil] cm/s [P < 0.05]) and vascular endothelial function (change of reactive hyperemia index from 1.36 to 1.56 and 1.89 [P < 0.05]). The change in reactive hyperemia index was significantly correlated with International Prostate Symptom Score, quality of life index and brachial-ankle pulse wave velocity. The improvement in intrapelvic blood flow by tadalafil can result in improved vascular endothelial function, in addition to improvement of voiding symptoms. The change in reactive hyperemia index seems to correlate with the severity of voiding symptoms, with tadalafil being most effective in patients with mild voiding symptoms.

Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing.

Calorie restriction (CR) in the absence of malnutrition exerts a multitude of physiological benefits with ageing in model organisms and in humans including improvements in vascular function. Despite the well-known benefits of chronic CR, long-term energy restriction is not likely to be a feasible healthy lifestyle strategy in humans due to poor sustained adherence, and presents additional concerns if applied to normal weight older adults. This review summarizes what is known about the effects of CR on vascular function with ageing including the underlying molecular 'energy- and nutrient-sensing' mechanisms, and discusses the limited but encouraging evidence for alternative pharmacological and lifestyle interventions that may improve vascular function with ageing by mimicking the beneficial effects of long-term CR.

Abstract 11847: Remote Ischemic Conditioning by Single Cuff Inflation Improves Aortic Elastic Properties and Endothelial Glycocalyx Thickness in Acute Myocardial Infarction Patients

Background: Remote ischemic conditioning attenuates ischemia-reperfusion injury in patients with STEMI. However, its effects on vascular function and biochemical mechanisms are not fully defined. Methods: We examined 110 patients with STEMI and 30 healthy controls. Patients were randomised in 2 remote ischemic conditioning protocols after a baseline assessment of vascular function (T0), a) one with two ischemic conditioning stimuli by brachial cuff inflation of both arms at 200mmHg for 5 min, separated by 15min, and each followed by vascular assessment (T1,T2), and a final vascular assessment (T3), 25 min after 2nd cuff deflation (double cuff inlation,n=60 ) or b) a second with omission of the second cuff inflation (single cuff inflation-n=50).In both protocols we measured a) the carotid-femoral pulse wave velocity (PWV);b)perfusion boundary region (PBR- micrometers) of the sublingual arterial microvessels as a marker of endothelial glycocalyx thickness;c) plasma malondialdehyde (MDA),NOx, and IL-6 levels as biomarkers of oxidative stress and inflammation. Results: The single cuff inflation protocol resulted in a more uniform aortic elasticity improvement (PWV T0: 12.09m/s, T1:11.74m/s, T2:11.59m/s, T3:11.81m/s),with the greatest difference measured at the last vascular assessment (T3: PWV= 11.8 single cuff vs 13.8 m/s double cuff inflation,p&lt;0.05).A greater glycocalyx integrity restoration was observed in patients with baseline PBR&gt; 2.1 in both protocols (mean difference in PBR improvement=0.5 at T1, p&lt;0.001).Conversely,in healthy controls, PWV and PBR remained unchanged throughout the study (p&gt;0.05).MDA was significantly reduced at T3 compared to baseline in STEMI(2.1 ± 0.15 at T3 vs 2.59 ±0.15 at T0, p&lt; 0.001) in both protocols while it remained unchanged in healthy controls. Additionally, the single cuff inflation protocol promoted a greater increase in NOx levels compared to the double inflation protocol (T0: 8.25± 1.18 to T3: 11.1 ± 2 μμ vs T0: 10.79± 1.18 to T3: 8.91±2 μμ, p&lt; 0.05). IL-6 levels were unaffected. Conclusion: Remote ischemic conditioning by a single 5-min cuff inflation, confers acute short-term improvement of vascular function, likely through oxidative stress reduction and nitrate- nitrite- NO pathway activation.

L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation

PurposeThe aim of this trial was to investigate the influence of a dietetic product consisting of a unique combination of l-arginine with the vitamins B6, folic acid and B12 (Telcor® Arginin plus) on endothelial dysfunction.MethodsSubjects aged 40–65 years with mild to moderate blood pressure (BP) elevation not treated with anti-hypertensive drugs were randomly assigned to either the dietetic product (n = 40) or a matching placebo (n = 41) for 3 months with open follow-up for a further 3 months. Postprandial change in endothelial function was assessed using the validated reactive hyperaemia index (RHI) at 3 months compared to the study onset (RHI post–pre, visit 3–visit 1; ΔΔRHI). Secondary parameters included BP and plasma homocysteine concentration.ResultsThe primary efficacy analysis revealed superiority of the nutritional intervention over placebo (p = 0.0349) in reducing the deterioration of endothelial function. While in the active group ΔΔRHI increased (0.371 ± 0.122), almost no change could be detected in the placebo group (0.031 ± 0.100), thus demonstrating a significant improvement in vascular function in the intervention group. Moreover, the intervention reduced BP and homocysteine levels. Non-serious adverse events were equally distributed in both groups, and none of the events were assessed as possibly intervention-related by the investigators.ConclusionsThis trial confirmed the effective and safe use of dietary management with l-arginine in combination with B vitamins. The primary efficacy analysis demonstrated a statistically significant superiority of the combination of l-arginine with B vitamins over placebo in improving and restoring impaired endothelial function and lowering BP in patients with mild to moderate blood pressure elevation.

Consumption of a flavonoid-rich açai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men

Açai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from açai consumption in humans is limited. The objective of the present study was to investigate the effect of açai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress. Twenty-three healthy male volunteers, aged 30-65 y and with a body mass index (in kg/m2) of 25-30, completed a randomized, controlled, high-fat challenge, double-blind, crossover, acute dietary intervention trial. The volunteers consumed either an açai-based smoothie (AS) or a macronutrient-matched control smoothie (PS) together with a high-fat breakfast meal challenge. The primary endpoint was the assessment of endothelial function in the brachial artery by flow-mediated dilatation (FMD). The acute consumption of an AS containing 694 mg total phenolics improved vascular function, with postprandial increases in FMD from baseline of 1.4% at 2 h compared with 0.4% after consumption of the PS (P = 0.001) and increases at 6 h of 0.8% for the AS compared with -0.3% for the PS (P < 0.001). There was also a significantly lower incremental area under the curve (iAUC) for total peroxide oxidative status after açai consumption relative to the control. No significant changes were observed in blood pressure, heart rate, or postprandial glucose response. However, the first postprandial insulin peak (after breakfast) and the iAUC for insulin were elevated for the AS relative to the PS. In this acute study in overweight men, açai consumption was associated with improvements in vascular function, which may lower the risk of a cardiovascular event. Future intervention studies, perhaps with a chronic design, in wider populations and with other biomarkers of disease risk are needed to fully elucidate the benefits of açai to health. This trial was registered at clinicaltrials.gov as NCT02292329.

Improvement of vascular function by magnetic nanoparticle-assisted circumferential gene transfer into the native endothelium

Gene therapy is a promising approach for chronic disorders that require continuous treatment such as cardiovascular disease. Overexpression of vasoprotective genes has generated encouraging results in animal models, but not in clinical trials. One major problem in humans is the delivery of sufficient amounts of genetic vectors to the endothelium which is impeded by blood flow, whereas prolonged stop-flow conditions impose the risk of ischemia.In the current study we have therefore developed a strategy for the efficient circumferential lentiviral gene transfer in the native endothelium under constant flow conditions. For that purpose we perfused vessels that were exposed to specially designed magnetic fields with complexes of lentivirus and magnetic nanoparticles thereby enabling overexpression of therapeutic genes such as endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF). This treatment enhanced NO and VEGF production in the transduced endothelium and resulted in a reduction of vascular tone and increased angiogenesis. Thus, the combination of MNPs with magnetic fields is an innovative strategy for site-specific and efficient vascular gene therapy.

PPARγ activation attenuates oxidative stress and improves cerebral arteries endothelial dysfunction in aging rat through up-regulating UCP2

Objectives: Increasing amounts of evidence implicate oxidative stress as having a pivotal role in age-related cerebrovascular dysfunction, which is an important risk factor for the development of cerebrovascular disease. Previous studies have shown that the activation of the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) in vascular endothelial cells results in an improvement of vascular function. Pioglitazone, a well-known PPAR-γ agonist, protects against oxidative stress in the rostral ventrolateral medulla by the upregulation of mitochondrial uncoupling protein 2 (UCP2).In this study, we sought to explore the effects and the underlying mechanisms of pioglitazone on age-related oxidative stress elevation and cerebrovascular dysfunction in aging rat cerebral arteries.

Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study.

Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. In a randomized crossover study, twenty healthy men (40-80 years) were supplemented with: (1) 70g dark chocolate (150 mg epicatechin) with placebo capsules; (2) pure epicatechin capsules (2 × 50 mg epicatechin) with 75g white chocolate; and (3) placebo capsules with 75 g white chocolate (0 mg epicatechin). Vascular function (flow-mediated dilation (FMD) and augmentation index (AIx)) were measured before and 2 hours after interventions. Epicatechin metabolites time-profiles were measured in blood to calculate the bioavailability. Pure epicatechin did not significantly improve FMD (+0.75%; p = 0.10) or AIx (-2.2%; p = 0.23) compared to placebo. Dark chocolate significantly improved FMD (+0.96%; p = 0.04) and AIx (-4.6%; p = 0.02). Differences in improvements in FMD (+ 0.21%; p = 0.65) or Aix (-2.4%; p = 0.20) between pure epicatechin and dark chocolate were not significant. The bioavailability of epicatechin did not differ between pure epicatechin and dark chocolate (p = 0.14). Despite differences in epicatechin dose, improvements in vascular function after pure epicatechin and chocolate were similar and the bioavailability did not differ, suggesting a role for epicatechin.

Cranberry (poly)phenol metabolites correlate with improvements in vascular function: A double-blind, randomized, controlled, dose-response, crossover study.

Cranberries are rich in potentially bioactive (poly)phenols. The aim of this paper was to investigate whether cranberry juice intake can improve vascular function in healthy men in a dose- and time-dependent manner, and to understand which of the circulating (poly)phenol metabolites correlate with vascular effects. A double-blind randomized controlled crossover trial was conducted in ten healthy males. Flow-mediated dilation (FMD), blood pressure, pulse wave velocity and augmentation index were investigated at baseline, 1, 2, 4, 6, and 8 h post-consumption of cranberry juices containing 409, 787, 1238, 1534, and 1910 mg of total cranberry (poly)phenols (TP), and a control drink. Plasma (poly)phenol metabolites were analyzed by UPLC-Q-TOF MS using authentic standards. We observed dose-dependent increases in FMD at 1, 2, 4, 6, and 8 h with a peak at 4 h and maximal effects with juice containing 1238 mg TP. A total of 60 metabolites were quantified in plasma after cranberry consumption. Twelve (poly)phenol metabolites significantly correlated with the increases in FMD, including ferulic and caffeic acid sulfates, quercetin-3-O-ß-D-glucuronide and a γ-valerolactone sulfate. (Poly)phenols in cranberry juice can improve vascular function in healthy males and this is linked to the presence of specific newly identified plasma metabolites.

Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms.

What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences. Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic stimuli (e.g. hormones, cytokines, blood-borne substances), which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebrovascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and the attenuation of their consequences. We provide an overview of the literature pertaining to the impact of repeated IPC on cardiovascular function, related to both local and remote adaptation, as well as potential clinical implications.

Can milk proteins be a useful tool in the management of cardiometabolic health? An updated review of human intervention trials

The prevalence of cardiometabolic diseases is a significant public health burden worldwide. Emerging evidence supports the inverse association between greater dairy consumption and reduced risk of cardiometabolic diseases. Dairy proteins may have an important role in the favourable impact of dairy on human health such as blood pressure (BP), blood lipid and glucose control. The purpose of this review is to update and critically evaluate the evidence on the impacts of casein and whey protein in relation to metabolic function. Evidence from short-term clinical studies assessing postprandial responses to milk protein ingestion suggests benefits on vascular function independent of BP, as well as improvement in glycaemic homeostasis. Long-term interventions have been less conclusive, with some showing benefits and others indicating a lack of improvement in vascular function. During chronic consumption BP appears to be lowered and both dyslipidaemia and hyperglacaemia seem to be controlled. Limited number of trials investigated the effects of dairy proteins on oxidative stress and inflammation. Although the underlying mechanisms of milk proteins on cardiometabolic homeostasis remains to be elucidated, the most likely mechanism is to improve insulin resistance. The incorporation of meals enriched with dairy protein in the habitual diet may result in the beneficial effects on cardiometabolic health. Nevertheless, future well-designed, controlled studies are needed to investigate the relative effects of both casein and whey protein on BP, vascular function, glucose homeostasis and inflammation.

Dietary polyphenols: Antioxidants or not?

Population studies have shown a strong association between dietary intake of polyphenols and reduced risk of cardiovascular disease. These associations have been confirmed to some extent by intervention studies which have shown improvements in vascular function and blood pressure with certain polyphenols or food extracts rich in polyphenols. The mechanisms involved in the bioactivity of dietary polyphenols is still under active investigation. It is unlikely that polyphenols act as antioxidants in vivo. Evidence suggests that dietary polyphenols or their metabolites act as signalling molecules and can increase nitric oxide bioavailability and induce protective enzymes. This review will outline some of the key issues in dietary polyphenol research that suggest mechanistic insights into the action of these bioactive compounds. There are a number of issues that remain to be resolved in bridging the gap between observational studies and intervention trials using food extracts or pure polyphenol compounds.

Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.

Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function.

Exercise training improves vascular function in adolescents with type 2 diabetes.

The impact of exercise training on vascular health in adolescents with type 2 diabetes has not been previously studied. We hypothesized that exercise training would improve micro‐ and macrovascular health in adolescents with type 2 diabetes. Thirteen adolescents (13–21 years, 10F) with type 2 diabetes were recruited from Princess Margaret Hospital. Participants were randomized to receive either an exercise program along with standard clinical care (n = 8) or standard care alone (n = 5). Those in the intervention group received 12 weeks of gym‐based, personalized, and supervised exercise training. Those in the control group were instructed to maintain usual activity levels. Assessments were conducted at baseline and following week 12. The exercise group was also studied 12 weeks following the conclusion of their program. Assessments consisted of conduit artery endothelial function (flow‐mediated dilation, FMD) and microvascular function (cutaneous laser Doppler). Secondary outcomes included body composition (dual‐energy X‐ray absorptiometry, DXA), glycemic control (whole body insulin sensitivity, M) assessed using the euglycemic–hyperinsulinemic clamp protocol, cardiorespiratory fitness (V˙O2peak), and muscular strength (1RM). Exercise training increased FMD (P < 0.05), microvascular function (P < 0.05), total lean mass (P < 0.05), and muscle strength (P < 0.001). There were no changes in cardiorespiratory fitness, body weight, BMI, or M. In the control group, body weight (P < 0.01), BMI (P < 0.01), and total fat mass (P < 0.05) increased. At week 24, improvements in vascular function were reversed. This study indicates that exercise training can improve both conduit and microvascular endothelial function and health, independent of changes in insulin sensitivity in adolescents with type 2 diabetes.

Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism

The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO)-dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 ± 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (∼13-52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via N(G)-monomethyl-L-arginine (L-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while L-NMMA and L-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 ± 2.2%, AA: 10.9 ± 2.5%, P = 0.01) and 12 kg (control: 9.5 ± 2.7%, AA: 15.9 ± 3.7%, P < 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm.

Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets.

Cardiovascular disease is often caused by endothelial cell (EC) dysfunction and atherosclerotic plaque formation at predilection sites. Also surgical procedures of plaque removal cause irreversible damage to the EC layer, inducing impairment of vascular function and restenosis. In the current study we have examined a potentially curative approach by radially symmetric re-endothelialization of vessels after their mechanical denudation. For this purpose a combination of nanotechnology with gene and cell therapy was applied to site-specifically re-endothelialize and restore vascular function. We have used complexes of lentiviral vectors and magnetic nanoparticles (MNPs) to overexpress the vasoprotective gene endothelial nitric oxide synthase (eNOS) in ECs. The MNP-loaded and eNOS-overexpressing cells were magnetic, and by magnetic fields they could be positioned at the vascular wall in a radially symmetric fashion even under flow conditions. We demonstrate that the treated vessels displayed enhanced eNOS expression and activity. Moreover, isometric force measurements revealed that EC replacement with eNOS-overexpressing cells restored endothelial function after vascular injury in eNOS(-/-) mice ex and in vivo. Thus, the combination of MNP-based gene and cell therapy with custom-made magnetic fields enables circumferential re-endothelialization of vessels and improvement of vascular function.

Cardiac and vascular changes with kidney transplantation

Cardiovascular event rates are high in patients with chronic kidney disease (CKD), increasing with deteriorating kidney function, highest in CKD patients on dialysis, and improve with kidney transplantation (KTx). The cardiovascular events in CKD patients such as myocardial infarction and heart failure are related to abnormalities of vascular and cardiac structure and function. Many studies have investigated the structural and functional abnormalities of the heart and blood vessels in CKD, and the changes that occur with KTx, but the evidence is often sparse and occasionally contradictory. We have reviewed the available evidence and identified areas where more research is required to improve the understanding and mechanisms of these changes. There is enough evidence demonstrating improvement of left ventricular hypertrophy, except in children, and sufficient evidence of improvement of left ventricular function, with KTx. There is reasonable evidence of improvement in vascular function and stiffness. However, the evidence for improvement of vascular structure and atherosclerosis is insufficient. Further studies are necessary to establish the changes in vascular structure, and to understand the mechanisms of vascular and cardiac changes, following KTx.

Antihypertensive effects of oleuropein-enriched olive leaf extract in spontaneously hypertensive rats.

The effects of chronic consumption of oleuropein-enriched (15% w/w) olive leaf extract (OLE) on blood pressure, endothelial function, and vascular oxidative and inflammatory status in spontaneously hypertensive rats (SHR) were evaluated. Ten Wistar Kyoto rats (WKY) and twenty SHR were randomly assigned to three groups: a control WKY group, a control SHR group and a SHR group treated with OLE (30 mg kg(-1)) for 5 weeks. Long-term administration of OLE reduced systolic blood pressure, heart rate, and cardiac and renal hypertrophy. OLE treatment reversed the impaired aortic endothelium-dependent relaxation to acetylcholine observed in SHR. OLE restored aortic eNOS phosphorylation at Ser-1177 and Thr-495 and increased eNOS activity. OLE eliminated the increased aortic superoxide levels, and reduced the elevated NADPH oxidase activity, as a result of reduced NOX-1 and NOX-2 mRNA levels in SHR. OLE reduced the enhanced vascular TLR4 expression by inhibition of mitogen-activated protein kinase (MAPK) signaling with the subsequent reduction of proinflammatory cytokines. In conclusion, OLE exerts antihypertensive effects on genetic hypertension related to the improvement of vascular function as a result of reduced pro-oxidative and pro-inflammatory status.