Acute high-intensity interval exercise versus moderate-intensity continuous exercise in heated water-based on hemodynamic, cardiac autonomic, and vascular responses in older individuals with hypertension.

OBJECTIVES: This crossover study design aimed to assess hemodynamic, cardiac autonomic, and vascular responses to high-intensity interval (HIIE) vs moderate-intensity continuous exercise (MICE) in older individuals with hypertension. METHODS: Twenty (67 ± 7 y) older individuals with hypertension were randomly assigned to perform HIIE, MICE, or control (CON) sessions in the heated swimming pool (30-32°C). Blood pressure (BP), arterial stiffness, endothelial reactivity, and heart rate variability (HRV) were measured pre, post, and 45 min (recovery) after each intervention followed by 24-h ambulatory BP and HRV. RESULTS: One single aerobic exercise session was not effective to provoke post-exercise hypotension and vascular improvements. HIIE was superior to MICE and CON to increasing parasympathetic modulation at post and recovery. Exercise sessions showed to disturb the autonomic system at nighttime compared to CON. CONCLUSIONS: These results may have important implications in water-based therapy and the elderly with hypertension.

Antioxidant and vasorelaxant effects of aqueous extract of large cardamom in L-NAME induced hypertensive rats.

PURPOSE: The present work aimed to study the effect of aqueous extract of large cardamom (AELC) to prevent vascular remodeling and oxidative stress in Nω-Nitro-L-arginine methyl ester (L-NAME)-induced hypertension. METHOD: Male Wistar rats were administered with L-NAME 40 mg/kg/day for 28 days by oral gavage. The treatments included captopril (20 mg/kg/day) or AELC (100, 200 and 400 mg/kg/day) along with L-NAME administration. RESULTS: L-NAME treated rats showed high systolic, diastolic and mean arterial pressure, decreased nitric oxide level, increased level of malondialdehyde in plasma, heart, aorta and kidney, hypertrophy of the vascular wall and reduced vascular response to acetylcholine in phenylephrine-precontracted aorta. Treatment with AELC markedly reduced the blood pressure, restored the nitric oxide level, reduced the malondialdehyde level, alleviated the hypertrophy in L-NAME-induced hypertensive rats. Additionally, it also improved the vascular response to acetylcholine in phenylephrine pre-contracted aorta. CONCLUSION: In conclusion, our results demonstrate the preventive effect of AELC in L-NAME-induced hypertensive model, which is possibly related to antioxidant activities and restoration of nitric oxide level.

Beneficial Effect of a Multistrain Synbiotic Prodefen® Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A.

A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen® Plus. MtS was induced by HFD (45%) in male Wistar rats. Half of the MtS animals received Prodefen® Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen® Plus supplementation did not affect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen® Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen® Plus could be considered an interesting non-pharmacological approach in MtS.

Mechanisms of pathophysiology of blood vessels in patients with multiple sclerosis treated with ozone therapy: a systematic review.

Multiple sclerosis (MS) defines as an intricate disease with numerous pathophysiological processes, including: inflammation, demyelination, oxidative stress, axonal damage, and repair mechanisms that interfere in this disease and highly related to the pathogenesis of MS. In parallel, recent studies have shown that the ozone administration could be very useful in treating neurological disorders and inflammatory and degenerative neurological diseases. In this review, we examine the recent literature on the pathophysiology of blood vessels in patients with multiple sclerosis treated with ozone therapy.

Synergistic mechanisms of Sanghuang-Danshen phytochemicals on postprandial vascular dysfunction in healthy subjects: A network biology approach based on a clinical trial.

With the increased risk of cardiovascular disease, the use of botanicals for vascular endothelial dysfunction has intensified. Here, we explored the synergistic mechanisms of Sanghuang-Danshen (SD) phytochemicals on the homeostatic protection against high-fat-induced vascular dysfunction in healthy subjects, using a network biology approach, based on a randomised crossover clinical trial. Seventeen differential markers identified in blood samples taken at 0, 3 and 6 h post-treatment, together with 12SD phytochemicals, were mapped onto the network platform, termed the context-oriented directed associations. The resulting vascular sub-networks illustrated associations between 10 phytochemicals with 32 targets implicated in 143 metabolic/signalling pathways. The three key events included adhesion molecule production (ellagic acid, fumaric acid and cryptotanshinone; VCAM-1, ICAM-1 and PLA2G2A; fatty acid metabolism), platelet activation (ellagic acid, protocatechuic acid and tanshinone IIA; VEGFA, APAF1 and ATF3; mTOR, p53, Rap1 and VEGF signalling pathways) and endothelial inflammation (all phytochemicals, except cryptotanshinone; 29 targets, including TP53 and CASP3; MAPK and PI3K-Akt signalling pathways, among others). Our collective findings demonstrate a potential of SD to protect unintended risks of vascular dysfunction in healthy subjects, providing a deeper understanding of the complicated synergistic mechanisms of signature phytochemicals in SD.

Vitamin D supplementation for the improvement of vascular function in patients with chronic kidney disease: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of vitamin D on vascular function remains controversial in chronic kidney disease (CKD) patients. The aim of the present work was to perform a meta-analysis of randomized controlled trials to evaluate the efficacy of vitamin D on vascular function in CKD patients. METHODS: We searched Medline, the Cochrane Central Register of Controlled Trials, Embase, the Science Citation Index, and clinical trial registries for randomized controlled trials comparing vitamin D with a placebo in CKD patients. RESULTS: We included seven trials. For flow-mediated dilation (FMD), there was no significant difference between the two groups (WMD 1.66%; 95% CI - 0.2 to 3.51, p = 0.08; with significant heterogeneity, p < 0.0001, I2 = 89%). We conducted a subgroup analysis. In the cholecalciferol group, compared with the placebo group, cholecalciferol significantly increased FMD (WMD 5.49%; 95% CI 4.36-6.62, p < 0.0001). In the 2 ug paricalcitol group, compared with the placebo group, paricalcitol significantly increased FMD (WMD 2.09%; 95% CI 1.28-2.9, p < 0.0001; without significant heterogeneity, p = 0.47, I2 = 0%). In the 1 ug paricalcitol group, there was no significant difference between the two groups. For pulse wave velocity (PWV), vitamin D significantly decreased PWV compared with the placebo (WMD - 0.93 m/s; 95% CI - 1.71 to - 0.15, p = 0.02; without significant heterogeneity, p = 0.14, I2 = 45%). For calcium (Ca) and parathyroid hormone (PTH), there was a significant difference between the vitamin D group and the placebo group. For 25-hydroxyvitamin D [25(OH)D], there was a significant difference between the inactive vitamin D group and the placebo group. For phosphorus (P), systolic blood pressure (SBP), and diastolic blood pressure (DBP), there were no significant differences between the two groups. CONCLUSIONS: We speculate that vitamin D might be able to improve vascular function in CKD patients. The effect of vitamin D might be associated with its doses and earlier stages of the disease might respond better to vitamin D. Furthermore, trials with larger populations and longer durations are needed in order to provide more reliable evidence.

Vasculature on the clock: Circadian rhythm and vascular dysfunction.

The master mammalian circadian clock (i.e. central clock), located in the suprachiasmatic nucleus of the hypothalamus, orchestrates the synchronization of the daily behavioural and physiological rhythms to better adapt the organism to the external environment in an anticipatory manner. This central clock is entrained by a variety of signals, the best established being light and food. However, circadian cycles are not simply the consequences of these two cues but are generated by endogenous circadian clocks. Indeed, clock machinery is found in mainly all tissues and cell types, including cells of the vascular system such as endothelial cells, fibroblasts, smooth muscle cells and stem cells. This machinery physiologically contributes to modulate the daily vascular function, and its disturbance therefore plays a major role in the pathophysiology of vascular dysfunction. Therapies targeting the circadian rhythm may therefore be of benefit against vascular disease.

Effects of aquarobic exercise and burdock intake on serum blood lipids and vascular elasticity in Korean elderly women.

BACKGROUND: The elderly's health issues are often complex and tend to lead to chronic diseases; such issues can be due to a fitness decline resulting from a lack of physical activities. The burdock root is a blood purifier, lymphatic system strengthener, and natural diuretic. The purpose of this study was to analyze the effects of aquarobic exercise and burdock intake on serum blood lipids and vascular elasticity in elderly women by implementing a 12-week program with these interventions. METHODS: Forty elderly female volunteer subjects aged 70 to 80years comprised the control group (n=8), aquarobic exercise group (n=11), aquarobic exercise and burdock intake combination group (n=11), and burdock intake group (n=10). The variables of serum blood lipids, and vascular elasticity were measured in all participants before and after the 12-week study. RESULTS: Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels significantly decreased in the aquarobic exercise group and aquarobic exercise and burdock intake combination group (p<0.05, p<0.01, p<0.001). No statistically significant changes in pulse wave velocity were also found within or between the groups before and after participation in the 12-week program. CONCLUSIONS: Our findings indicate that aquarobic exercise and burdock intake improved the serum blood lipid levels and vascular elasticity of Korean elderly women. Additionally, burdock extract intake may be useful in vascular health by playing a secondary role in disease prevention and health promotion.

Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function.

Nowadays dietary flavonoids attract much attention in the prevention of chronic diseases. Epidemiological and intervention studies strongly suggest that flavonoid intake has beneficial effects on vascular health. It is unlikely that flavonoids act as direct antioxidants, although oxidative stress profoundly contributes to vascular impairment leading to cardiovascular diseases. Instead, flavonoids may exert their function by tuning the cellular redox state to an adaptive response or tolerable stress. However, the optimum intake of flavonoids from supplements or diet has not been clarified yet, because a number of exogenous and endogenous factors modulating their bioavailability affect their vascular function. This review will focus on the current knowledge of the bioavailability and vascular function of quercetin as a representative of antioxidative flavonoids. Current intervention studies imply that intake of quercetin-rich onion improves vascular health. Onion may be superior to quercetin supplement from the viewpoint of quercetin bioavailability, probably because the food matrix enhances the intestinal absorption of quercetin. α-Glucosylation increases its bioavailability by elevating the accessibility to the absorptive cells. Prenylation may enhance bioaccumulation at the target site by increasing the cellular uptake. However, these chemical modifications do not guarantee health benefits to the vascular system. Dietary quercetin is exclusively present as their conjugated form in the blood stream. Quercetin may exert its vascular function as an aglycone within macrophage cells after inflammation-induced deconjugation and as conjugated metabolites by targeting endothelial cells. The relationship between the bioavailability and bio-efficacy should be clarified, to evaluate the vascular function of a wide variety of dietary flavonoids.

Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: Relevance for cardiovascular outcomes.

AIMS: To overview the effects of omega-3 polyunsaturated fatty acids (PUFA) on blood vessels and blood pressure (BP) and their relevance for cardiovascular prevention. DATA SYNTHESIS: The importance of omega-3 PUFA for the cardiovascular system has come under the spotlight during the last decades. These fatty acids are present in variable amounts in cell membranes of mammal species, and their content affects a variety of cellular functions. Evidence obtained in animal and human studies suggests that omega-3 PUFA affect many steps of the atherosclerotic process. In blood vessels, omega-3 PUFA improve endothelial function; promote vasodilatation through relaxation of smooth muscle cells; exert antioxidant, anti-inflammatory, and antithrombotic actions; delay development of plaques and increase their stability; and decrease wall stiffening. Omega-3 PUFA might affect BP, and studies conducted with ambulatory monitoring suggest that supplementation with these fatty acids decreases the average 24-h BP levels. This effect on BP is related to the pretreatment membrane content of omega-3 PUFA, and this might explain some inconsistencies among intervention trials. Meta-analyses indicate that omega-3 PUFA have a mild but significant BP lowering effect. While encouraging results were initially obtained with the use of omega-3 PUFA supplements in secondary prevention trials, meta-analyses have not confirmed the ability of these fatty acids to decrease the risk of coronary heart and cerebrovascular disease. CONCLUSIONS: Omega-3 PUFA are associated with significant improvement in vascular function and lowering of BP. However, the evidence currently supporting the role of these fatty acids in cardiovascular prevention is weak and needs further investigation.

Meditation can produce beneficial effects to prevent cardiovascular disease.

Coronary heart disease is the major cause of global cardiovascular mortality and morbidity. Lifestyle behaviour contributes as a risk factor: unhealthy diet, sedentary lifestyle, tobacco, alcohol, hypertension, diabetes, dyslipidemia and psychosocial stress. Atherosclerosis pathologic mechanisms involving oxidative stress, dyslipidemia, inflammation and senescence are associated with arterial wall damage and plaque formation. Stress reduction was observed in several types of meditation. After meditation, hormonal orchestration modulates effects in the central nervous system and in the body. All types of meditation are associated with blood pressure control, enhancement in insulin resistance, reduction of lipid peroxidation and cellular senescence, independent of type of meditation. This review presents scientific evidence to explain how meditation can produce beneficial effects on the cardiovascular system, and particularly regarding vascular aspects.

Consuming a balanced high fat diet for 16 weeks improves body composition, inflammation and vascular function parameters in obese premenopausal women.

OBJECTIVE: Inflammation, insulin resistance and vascular dysfunction characterize obesity and predict development of cardiovascular disease (CVD). Although women experience CVD events at an older age, vascular dysfunction is evident 10years prior to coronary artery disease. Questions remain whether replacing SFA entirely with MUFA or PUFA is the optimal approach for cardiometabolic benefits. This study tested the hypotheses that: a) body composition, inflammation and vascular function would improve with a high fat diet (HFD) when type of fat is balanced as 1/3 SFA, 1/3 MUFA and 1/3 PUFA; and b) body composition, inflammation and vascular function would improve more when balanced HFD is supplemented with 18C fatty acids, in proportion to the degree of 18C unsaturation. METHODS: Obese premenopausal women were stabilized on balanced HFD and randomized to consume 9g/d of encapsulated stearate (18:0), oleate (18:1), linoleate (18:2) or placebo. RESULTS: Significant improvements occurred in fat oxidation rate (↑6%), body composition (%fat: ↓2.5±2.1%; %lean: ↑2.5±2.1%), inflammation (↓ IL-1α, IL-1ß, 1L-12, Il-17, IFNγ, TNFα, TNFß) and vascular function (↓BP, ↓PAI-1, ↑tPA activity). When compared to HFD+placebo, HFD+stearate had the greatest effect on reducing IFNγ (↓74%) and HFD+linoleate had the greatest effect on reducing PAI-1 (↓31%). CONCLUSIONS: Balancing the type of dietary fat consumed (SFA/MUFA/PUFA) is a feasible strategy to positively affect markers of CVD risk. Moreover, reductions in inflammatory molecules involved in vascular function might be enhanced when intake of certain 18C fatty acids is supplemented. Long term effects need to be determined for this approach.

Restoring vascular function with hyperbaric oxygen treatment: recovery mechanisms.

Treatment with hyperbaric oxygen can be a beneficial adjuvant therapy in various disorders characterized by compromised tissue oxygenation and perfusion. However, the effects of hyperbaric oxygenation cannot be simply explained as a compensation of the oxygen deficit. Hyperbaric oxigenation has a much broader influence and has the ability to alter protein expression, modulate signaling pathways and affect vascular structure and function. We discuss some of the most important uses of hyperbaric oxigenation for clinical conditions that involve abnormal vascular function. We present recent studies and insights into the mechanisms and effects of hyperbaric oxygen in the vasculature.

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERß and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD.

Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment.

Mutations in the coding sequence of the X-linked gene MeCP2 (Methyl CpG-binding protein) are present in around 80% of patients with Rett Syndrome, a common cause of intellectual disability in female and to date without any effective pharmacological treatment. A relevant, and so far unexplored feature of RTT patients, is a marked reduction in peripheral circulation. To investigate the relationship between loss of MeCP2 and this clinical aspect, we used the MeCP2 null mouse model B6.129SF1-MeCP2tm1Jae for functional and pharmacological studies. Functional experiments were performed on isolated resistance mesenteric vessels, mounted on a pressurized myograph. Vessels from female MeCP2(+/-) mice show a reduced endothelium-dependent relaxation, due to a reduced Nitric Oxide (NO) availability secondary to an increased Reactive Oxygen Species (ROS) generation. Such functional aspects are associated with an intravascular increase in superoxide anion production, and a decreased vascular eNOS expression. These alterations are reversed by curcumin administration (5% (w/w) dietary curcumin for 21 days), which restores endothelial NO availability, decreases intravascular ROS production and normalizes vascular eNOS gene expression. In conclusion our findings highlight alterations in the vascular/endothelial system in the absence of a correct function of MeCP2, and uncover related cellular/molecular mechanisms that are rescued by an anti-oxidant treatment.

Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis.

Vasopressin analogs are used as a supplement to norepinephrine in septic shock. The isolated effects of vasopressin agonists on sepsis-induced vascular dysfunction, however, remain controversial. Because V(2)-receptor stimulation induces vasodilation and procoagulant effects, a higher V(1a)- versus V(2)-receptor selectivity might be advantageous. We therefore hypothesized that a sole, titrated infusion of the selective V(1a)-agonist Phe(2)-Orn(8)-Vasotocin (POV) is more effective than the mixed V(1a)-/V(2)-agonist AVP for the treatment of vascular and cardiopulmonary dysfunction in methicillin resistant staphylococcus aureus pneumonia-induced, ovine sepsis. After the onset of hemodynamic instability, awake, chronically instrumented, mechanically ventilated, and fluid resuscitated sheep were randomly assigned to receive continuous infusions of either POV, AVP, or saline solution (control; each n = 6). AVP and POV were titrated to maintain mean arterial pressure above baseline - 10 mmHg. When compared with that of control animals, AVP and POV reduced neutrophil migration (myeloperoxidase activity, alveolar neutrophils) and plasma levels of nitric oxide, resulting in higher mean arterial pressures and a reduced vascular leakage (net fluid balance, chest and abdominal fluid, pulmonary bloodless wet-to-dry-weight ratio, alveolar and septal edema). Notably, POV stabilized hemodynamics at lower doses than AVP. In addition, POV, but not AVP, reduced myocardial and pulmonary tissue concentrations of 3-nitrotyrosine, VEGF, and angiopoietin-2, thereby leading to an abolishment of cumulative fluid accumulation (POV, 9 ± 15 ml/kg vs. AVP, 110 ± 13 ml/kg vs. control, 213 ± 16 ml/kg; P < 0.001 each) and an attenuated cardiopulmonary dysfunction (left ventricular stroke work index, PaO(2)-to-FiO(2) ratio) versus control animals. Highly selective V(1a)-agonism appears to be superior to unselective vasopressin analogs for the treatment of sepsis-induced vascular dysfunction.