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1.
Int J Sports Med ; 41(3): 141-153, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31935777

RESUMO

This study analyzed the effects of physical exercise interventions on cardiovascular endpoints in childhood cancer survivors. Relevant articles were systematically searched in PubMed, CINAHL, and Web of Science databases (since inception to 11th September 2019). We performed a meta-analysis (random effects) to determine the mean difference (expressed together with 95% confidence intervals) between pre- and post-intervention values for those cardiovascular endpoints reported in more than three studies. Twenty-seven studies (of which 16 were controlled studies) comprising 697 participants were included. Only three studies reported adverse events related to exercise interventions. Exercise resulted in an increased performance on the 6-minute walk distance test (mean difference=111 m, 95% confidence interval=39-183, p=0.003) and a non-significant trend (mean difference=1.97 ml∙kg-1∙min-1, 95% confidence interval=-0.12-4.06, p=0.065) for improvement in peak oxygen uptake. Furthermore, left ventricular ejection fraction was preserved after exercise interventions (mean difference=0.29%, 95% confidence interval=-1.41-1.99, p=0.738). In summary, exercise interventions might exert a cardioprotective effect in childhood cancer survivors by improving - or attenuating the decline of - physical capacity and cardiovascular function. Further studies, particularly randomized controlled trials, are needed to confirm these benefits.


Assuntos
Sobreviventes de Câncer , Aptidão Cardiorrespiratória/fisiologia , Terapia por Exercício , Pressão Sanguínea/fisiologia , Criança , Endotélio Vascular/fisiologia , Teste de Esforço , Frequência Cardíaca/fisiologia , Humanos , Consumo de Oxigênio/fisiologia , Volume Sistólico/fisiologia
2.
Life Sci ; 245: 117357, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31991180

RESUMO

AIMS: Schisandra is a good choice in Traditional Chinese Medicine for the therapy of cardiovascular diseases, but whether it contains a or some specific component (s) responsible these effects are still unclear. In the present study, we explored whether Schisantherin A (SCA) causes vasorelaxation in isolated rat thoracic aorta. MAIN METHODS: We selected SCA, one of the main monomers of lignans from Schisandra, to examine its vasorelaxant effect on the isolated rat thoracic aorta and also exploited several tool inhibitors to probe its underlying mechanisms. KEY FINDINGS: SCA produced relaxation concentration-dependently on the endothelium-intact (43.56 ± 2.17%) and endothelium-denuded thoracic aorta strips (18.76 ± 3.95%) pre-contracted by phenylephrine (PE). However, after treated with indomethacin or L-NAME, SCA showed only partial vasorelaxant effects. Whereas, this vasorelaxation by SCA was not changed with specific K+-channel inhibitors, i.e. barium chloride (BaCl2), 4-aminopyridine (4-AP), tetraethylamine (TEA), and glibenclamide. SCA had no effect on the aorta strips pre-contracted by PE in neither Ca2+-free nor CaCl2 conditions. But, in the Ca2+ free and high K+ environment, SCA partly abolished the vasocontraction induced by CaCl2. SIGNIFICANCE: It was the first report to demonstrate that SCA had endothelium-dependent and -independent vasorelaxant effects on the isolated rat thoracic aorta, and the underlying mechanisms might be involved into its promoting the production of nitric oxide (NO) and prostacyclin (PGI2), and inhibiting the voltage-dependent calcium channels (VDCCs) opening. This study may partially explain the use of Schisandra in cardiovascular diseases and facilitate further drug development as well.


Assuntos
Aorta Torácica/efeitos dos fármacos , Ciclo-Octanos/farmacologia , Dioxóis/farmacologia , Endotélio Vascular/efeitos dos fármacos , Lignanas/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta Torácica/fisiologia , Western Blotting , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Endotélio Vascular/fisiologia , Masculino , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
J Agric Food Chem ; 68(7): 1871-1876, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31294557

RESUMO

Cocoa flavanols (CFs) can improve flow-mediated dilation (FMD), blood pressure, and vascular stiffness in healthy subjects. Endothelial microparticles (EMPs) are markers of endothelial functional integrity, reflecting activation and injury. In plasma samples, we investigated whether age-dependent changes in circulating EMPs exist and whether CFs decrease EMPs in healthy humans. The concentrations of CD31+/41-, CD144+, and CD62e+ EMPs (flow cytometry) were increased in healthy elderly (n = 19) compared to young (n = 20) non-smokers. EMPs correlated with age, systolic blood pressure, and pulse wave velocity. CD31+/41- and CD62e+ EMPs inversely correlated with FMD. Following 2 weeks twice-daily CF consumption (450 mg), CD31+/41- and CD144+ EMPs decreased in both young and elderly subjects compared to the CF-free control. The EMP decrease inversely correlated with FMD improvements. Cardiovascular aging is associated with increased EMPs that can be modulated by dietary flavanols along with improvements in vascular function. This indicates that flavanol consumption can improve endothelial functional integrity in healthy humans.


Assuntos
Cacau/metabolismo , Endotélio Vascular/fisiologia , Flavanonas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Micropartículas Derivadas de Células/química , Selectina E/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Onda de Pulso , Rigidez Vascular , Vasodilatação , Adulto Jovem
4.
Food Funct ; 10(10): 6322-6330, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31524216

RESUMO

BACKGROUND: Several intervention studies have investigated the relationship between cocoa flavanols and endothelial function. However, the shape of the association and the type of compounds responsible for the effects are largely unknown. OBJECTIVE: To examine the dose-response association between the consumption of cocoa flavanols and endothelial function, measured by flow-mediated dilation (FMD). DESIGN: Two investigators searched Scopus® for the relevant human intervention studies, which were pooled and meta-analysed. Heterogeneity in the findings was explored with various subgroup analyses. RESULTS: Fifteen published articles with 18 intervention arms met the inclusion criteria. Participants in these intervention groups received 80 to 1248 mg (mean: 704 mg) more flavanols than control groups. A significant improvement of FMD by 1.17% (95% CI: 0.76% to 1.57%) was calculated, with strong evidence of a non-linear association (inverted U-shape) between cocoa flavanols and FMD. CONCLUSIONS: This meta-analysis provides evidence that cocoa flavanols could significantly improve endothelial function, with an optimal effect observed with 710 mg total flavanols, 95 mg (-)-epicatechin or 25 mg (+)-catechin. However, there was substantial variation in the results that could not be explained by the characteristics that we explored, and there were significant risk-of-bias concerns with a large majority of the studies.


Assuntos
Cacau/metabolismo , Endotélio Vascular/fisiologia , Flavonóis/metabolismo , Adulto , Idoso , Pressão Sanguínea , Cacau/química , Chocolate/análise , Feminino , Flavonóis/análise , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Nutrients ; 11(8)2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390819

RESUMO

Peach (Prunus persica (L.) Batsch) is a popular fruit consumed by people worldwide, owing to its pleasant flavor and high mineral nutrient content. A few plants from the genus Prunus, such as Prunus yedoensis, Prunus cerasus, and Prunus serotina have shown vasorelaxant and vasodilatory effects, to date, no study has investigated the vasorelaxation effects of the P. persica branch extract (PPE). The vasorelaxant effect of PPE was endothelium-dependent, and it was related to the NO-sGC-cGMP, vascular prostacyclin, and muscarinic receptor transduction pathway. K+ channels, such as the BKCa, KV, and KATP channels, were partially associated with PPE-induced vasorelaxation. PPE was effective in relaxing serotonin (5-HT)- or angiotensin II-induced contraction; furthermore, PPE attenuated Ca2+-induced vasoconstriction by IP3 receptors in the SR membrane, but its vasorelaxant effect was not associated with the influx of extracellular Ca2+ via receptor-operative Ca2+ channels or voltage-dependent Ca2+ channels. Recognizing the rising use of functional foods for hypertension treatment, our findings imply that PPE may be a natural antihypertensive agent.


Assuntos
Aorta Torácica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Prunus persica/química , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Masculino , Osteocondrodisplasias , Extratos Vegetais/química , Ratos , Vasodilatadores/química
6.
Phytother Res ; 33(11): 2989-2995, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31423626

RESUMO

Impaired endothelial function is an important risk factor for cardiovascular disease (CVD). Curcumin supplementation might be an appropriate approach to decrease the complications of CVD. Randomized controlled trials assessing the effects of curcumin supplementation on endothelial function were included. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science with no time restriction. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. Between-study heterogeneities were estimated using the Cochran's Q test and I-square (I2 ) statistic. Data were pooled using a random-effects model, and weighted mean differences (WMDs) were considered as the overall effect sizes. Ten studies with 11 effect sizes were included. We found a significant increase in flow-mediated dilation (FMD) following curcumin supplementation (WMD: 1.49; 95% CI [0.16, 2.82]). There was no effect of curcumin supplement on pulse wave velocity (PWV; WMD: -41.59; 95% CI [-86.59, 3.42]), augmentation index (Aix; WMD: 0.71; 95% CI [-1.37, 2.79]), endothelin-1 (ET-1; WMD: -0.30; 95% CI [-0.96, 0.37]), and soluble intercellular adhesion molecule-1 (sICAM-1; WMD: -10.11; 95% CI [-33.67, 13.46]). This meta-analysis demonstrated the beneficial effects of curcumin supplementation on improving FMD, though it did not influence PWV, Aix, Et-1, and sICAM-1.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Curcumina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Idoso , Doenças Cardiovasculares/fisiopatologia , Suplementos Nutricionais , Endotélio Vascular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
7.
Adv Exp Med Biol ; 1155: 407-414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468418

RESUMO

High-intensity resistance exercise has been shown to increase arterial stiffness and reduce vascular endothelial function. Taurine supplementation has a favorable effect on maintaining vascular function. We had previously reported that taurine supplementation attenuated increases in resistance exercise-induced arterial stiffness. In the present study, we further investigate the effects of taurine supplementation on vascular endothelial function at rest and after resistance exercise.Twenty-nine healthy men were recruited and randomly assigned to either the placebo supplement group (n = 14) or the taurine supplement group (n = 15) in a double-blinded manner. Subjects were required to ingest 6 g of either a placebo or the taurine supplement for 2 weeks prior to and 3 days following the exercise. Two weeks after the commencement of supplementation, the subjects were asked to perform 2 sets of 20 repetitive unilateral maximal-effort resistance exercise of the elbow flexors on a Biodex isokinetic dynamometer, with each contraction lasting 3 s, with 1 repetition performed every 9 s and 4 min rest in between sets. We evaluated the changes in brachial artery flow-mediated dilation (FMD) in the non-exercised arm as an index of vascular endothelial function. Relative and absolute FMDs were measured prior to supplementation, before exercise, and 24, 48, and 96 h after exercise.Two weeks of taurine supplementation significantly increased both relative and absolute FMDs. Baseline diameter significantly increased at 96 h following the exercise in both groups. However, there was no change in the peak diameter. Consequently, both relative and absolute FMDs were significantly reduced at 96 h after the exercise in both groups. Taurine supplementation does not affect resistance exercise-induced reduction in FMD.Two weeks of taurine supplementation (6 g/day) significantly increased vascular endothelial function at rest; however, taurine supplementation did not improve resistance exercise-induced reduction in FMD.


Assuntos
Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Treinamento de Resistência , Taurina/farmacologia , Vasodilatação , Artéria Braquial , Endotélio Vascular/fisiologia , Humanos , Masculino
8.
Nutrients ; 11(8)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382524

RESUMO

: Dietary nitrate (NO3-) has been reported to improve endothelial function (EF) and blood pressure (BP). However, most studies only assess large-vessel EF with little research on the microvasculature. Thus, the aim of the present pilot study is to examine NO3- supplementation on microvascular and large-vessel EF and BP. Twenty older adults (63 ± 6 years) were randomized to a beetroot juice (BRJ) or placebo (PLA) group for 28 (±7) days and attended three laboratory visitations. Across visitations, blood pressure, microvascular function and large-vessel EF were assessed by laser Doppler imaging (LDI) with iontophoresis of vasoactive substances and flow-mediated dilatation (FMD), respectively. Plasma NO3-concentrations, BP and the presence of NO3- reducing bacteria were also assessed. Plasma NO3- increased following two weeks of BRJ supplementation (p = 0.04) along with a concomitant decrease in systolic and diastolic BP of approximately -6 mmHg and -4 mmHg, respectively (p = 0.04; p = 0.01, respectively). BP remained unchanged in the PLA group. There were no significant differences in endothelium-dependent or endothelium-independent microvascular responses between groups. FMD increased by 1.5% following two weeks of BRJ (p = 0.04), with only a minimal (0.1%) change for the PLA group. In conclusion, this pilot study demonstrated that medium-term BRJ ingestion potentially improves SBP, DBP and large-vessel EF in healthy older adults. The improvements observed in the present study are likely to be greater in populations presenting with endothelial dysfunction. Thus, further prospective studies are warranted in individuals at greater risk for cardiovascular disease.


Assuntos
Beta vulgaris/química , Pressão Sanguínea/fisiologia , Endotélio Vascular/fisiologia , Sucos de Frutas e Vegetais , Microvasos/fisiologia , Nitratos/administração & dosagem , Idoso , Disponibilidade Biológica , Pressão Sanguínea/efeitos dos fármacos , Dieta , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Masculino , Microvasos/efeitos dos fármacos , Pessoa de Meia-Idade , Nitratos/farmacocinética , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacocinética , Nitritos/administração & dosagem , Nitritos/metabolismo , Projetos Piloto , Placebos , Raízes de Plantas/química
9.
Growth Factors ; 37(1-2): 53-67, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31284789

RESUMO

Angiogenic blood vessel growth is essential to ensure organs receive adequate blood supply to support normal organ function and homeostasis. Angiogenesis involves a complex series of cellular events through which new vessels grow out from existing vasculature. Growth factor signaling, layered over a range of other signaling inputs, orchestrates this process. The response of endothelial cells (ECs) to growth factor signals must be carefully controlled through feedback mechanisms to prevent excessive vessel growth, remodeling or destabilization. In this article, we summarize recent findings describing how ECs respond to growth factor signals during blood vessel development and homeostasis and how perturbation of these responses can lead to disease.


Assuntos
Neovascularização Fisiológica , Transdução de Sinais , Doenças Vasculares/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Endotélio Vascular/crescimento & desenvolvimento , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Humanos , Doenças Vasculares/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética
10.
J Atheroscler Thromb ; 26(8): 688-696, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31270300

RESUMO

Bilirubin is a fundamental metabolic end product of heme degradation. Despite acting as a cytotoxic metabolite at high concentrations, bilirubin at physiological concentrations has antioxidant effects, such as scavenging reactive oxygen species, leading to a decrease in oxidative stress. Endothelial dysfunction is an early feature of and plays an important role in the development and progression of atherosclerosis, leading to cardiovascular complications. One mechanism of endothelial dysfunction is an increase in oxidative stress, by which the bioavailability of nitric oxide is decreased. Therefore, bilirubin is expected to improve endothelial function, to inhibit the progression of atherosclerosis, and to reduce cardiovascular complications by inactivating oxidative stress through its antioxidant effects. In this review, we will focus on the clinical associations of the antioxidant bilirubin with endothelial function and cardiovascular complications.


Assuntos
Antioxidantes/metabolismo , Bilirrubina/metabolismo , Endotélio Vascular/fisiologia , Doenças Vasculares/fisiopatologia , Animais , Endotélio Vascular/citologia , Humanos
11.
J Ethnopharmacol ; 243: 112118, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31351191

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia forficata Link, commonly known as "cow's paw", is a native plant from South America. Its leaves are widely used in Brazilian folk medicine to treat diabetes and cardiovascular disorders. Although this species' biological potential has been extensively proven as an antidiabetic, anti-inflammatory and antioxidant agent, there is a lack of studies to evidence its action on the cardiovascular system. AIM OF THE STUDY: This study was designed to investigate the vascular effects of B. forficata leaves preparations and its majority compound kaempferitrin, as well as its aglycone form kaempferol, in rat aortic rings of normotensive (NTR) and hypertensive (SHR) rats. MATERIALS AND METHODS: Aorta rings from NTR and SHR precontracted with phenylephrine were exposed to cumulative concentrations of B. forficata extract, fractions (1-50 µg/mL) and compounds (0.001-0.3 µg/mL). The mechanisms involved in the vasorelaxant effect of ethyl-acetate plus butanol fraction (EAButF) were also evaluated. RESULTS: Although kaempferitrin is the most abundant compound found in both methanolic extract and EAButF, 24 minor phenolic compounds were identified in B. forficata leaves, including kaempferol. EAButF was the only with endothelium-dependent and independent vasorelaxant properties in both NTR and SHR. The incubation with L-NAME or ODQ completely blocked EAButF-induced vasorelaxation. On the other hand, the incubation with propranolol, atropine, indomethacin, glibenclamide or barium chloride did not change the vasorelaxant activity of EAButF (50 µg/mL). Nevertheless, the incubation with tetraethylammonium and 4-aminopyridine significantly influenced the EAButF activity. It was also shown that Ca2+ influx or efflux is not related to EAButF vasorelaxation potential. Kaempferitrin and kaempferol were also able to relax the rat aortic rings in 34.70% and 40.54%, respectively. CONCLUSIONS: This study shows, for the first time, the vasorelaxant effect of EAButF from B. forficata leaves, an effect that may be attributed to the modulation of vascular tone through nitric oxide/soluble guanylate cyclase pathway, and potassium channels. The bioactive kaempferitrin and kaempferol seem to be important for the effects observed with the fraction. Finally, preparations obtained from the leaves of B. forficata may be interesting candidates for new or complementary strategies regarding cardiovascular diseases.


Assuntos
Aorta Torácica/efeitos dos fármacos , Bauhinia , Hipertensão/fisiopatologia , Extratos Vegetais/farmacologia , Vasodilatadores/farmacologia , Animais , Aorta Torácica/fisiologia , Brasil , Doenças Cardiovasculares/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Técnicas In Vitro , Quempferóis/farmacologia , Masculino , Medicina Tradicional , Óxido Nítrico/fisiologia , Folhas de Planta , Plantas Medicinais , Canais de Potássio/fisiologia , Ratos Endogâmicos SHR , Ratos Wistar
12.
Biofabrication ; 11(4): 045009, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31220824

RESUMO

Engineered tubular constructs made from soft biomaterials are employed in a myriad of applications in biomedical science. Potential uses of these constructs range from vascular grafts to conduits for enabling perfusion of engineered tissues and organs. The fabrication of standalone tubes or complex perfusable constructs from biofunctional materials, including hydrogels, via rapid and readily accessible routes is desirable. Here we report a methodology in which customized coaxial nozzles are 3D printed using commercially available stereolithography (SLA) 3D printers. These nozzles can be used for the fabrication of hydrogel tubes via coextrusion of two shear-thinning hydrogels: an unmodified Pluronic® F-127 (F127) hydrogel and an F127-bisurethane methacrylate (F127-BUM) hydrogel. We demonstrate that different nozzle geometries can be modeled via computer-aided design and 3D printed in order to generate tubes or coaxial filaments with different cross-sectional geometries. We were able to fabricate tubes with luminal diameters or wall thicknesses as small as ∼150 µm. Finally, we show that these tubes can be functionalized with collagen I to enable cell adhesion, and human umbilical vein endothelial cells can be cultured on the luminal surfaces of these tubes to yield tubular endothelial monolayers. Our approach could enable the rapid fabrication of biofunctional hydrogel conduits which can ultimately be utilized for engineering in vitro models of tubular biological structures.


Assuntos
Endotélio Vascular/fisiologia , Hidrogéis/farmacologia , Modelos Biológicos , Impressão Tridimensional , Animais , Endotélio Vascular/efeitos dos fármacos , Fluorescência , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Ratos
13.
Eur J Appl Physiol ; 119(8): 1809-1818, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190212

RESUMO

INTRODUCTION: Retrograde shear causes endothelial damage and is pro-atherogenic. The purpose of our study was to examine the impact of vascular remodeling from habitual exercise training on acute changes in retrograde shear and microvascular oxygenation (SMO2) induced via 30 min of external compression. METHODS: Participants included 11 exercise trained (ET) men (Division I track athletes; age 20 ± 3 years) and 18 recreationally active (RA) men (age 23 ± 5 years). Near-infrared spectroscopy (NIRS) was used to measure vastus medialis SMO2. Doppler-ultrasound was used to assess SFA intima-media thickness, diameter and flow velocity to derive retrograde shear. Vascular measures were made at baseline (BASELINE), during a sham condition (calf compression to 5 mmHg, SHAM) and during the experimental condition (calf compression to 60 mmHg, EXP). RESULTS: Compared to RA, ET had larger SFA diameters (0.66 ± 0.06 vs 0.58 ± 0.06 cm, p < 0.05) and lower SFA IMT (0.33 ± 0.03 vs 0.36 ± 0.07 mm, p < 0.05). Retrograde shear increased similarly in both groups during EXP (p < 0.05) but ET men had lower overall retrograde shear during the conditions (BASELINE 75.8 ± 26.8 vs EXP 88.2 ± 16.9 s-1) compared to RA men (BASELINE 84.4 ± 23.3 vs EXP 106.4 ± 19.6 s-1p < 0.05). There was a similar increase in SMO2 from BASELINE to SHAM (ET + 8.1 ± 4.8 vs RA + 6.4 ± 9.7%) and BASELINE to EXP (ET + 8.7 ± 6.4 vs RA + 7.1 ± 9.0%) in both groups. CONCLUSION: Beneficial vascular remodeling in ET men is associated with lower retrograde shear during external compression. Acute increases in retrograde shear with external compression do not detrimentally impact microvascular oxygenation.


Assuntos
Exercício , Hemodinâmica , Músculo Esquelético/fisiologia , Consumo de Oxigênio , Reperfusão , Adolescente , Adulto , Bandagens Compressivas , Endotélio Vascular/fisiologia , Artéria Femoral/fisiologia , Humanos , Masculino , Microvasos/fisiologia , Músculo Esquelético/irrigação sanguínea
14.
Chem Biol Interact ; 309: 108710, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31199930

RESUMO

Formic acid is a common organic acid used in many industrial processes. There is a paucity of research on the direct toxicity of formic acid and how it might affect the cardiovascular system. This study aimed to understand the effect of formic acid on vascular tension in an animal model and the underlying mechanism. Results found that the vasodilation induced by formic acid was related to the endothelium. When the dosage of formic acid was 1 mM or 5 mM, the vasodilation of endothelium-intact rings was partially suppressed by l-NAME, NS-2028 and nifedipine, and vasoconstriction caused by CaCl2 was inhibited, and the mRNA levels of eNOS, the activity of NOS (tNOS, iNOS and cNOS) and the level of NO and cGMP were significantly increased. Results also found that eNOS protein expression was significantly enhanced by 5 mM of formic acid. These results suggest formic acid can relax the aortic vessels of rats in a dose-dependent pattern. Further, the mechanism of the formic acid-induced vasodilatation likely involved the NO/cGMP pathway. Finally, the current study has revealed that vasodilation induced by high concentrations of formaldehyde may be the effect of the metabolite formic acid. This study will help further inform the etiologies of formic acid-related angiocardiopathies.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Formiatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Animais , Canais de Cálcio Tipo L/metabolismo , Cloreto de Cálcio/farmacologia , GMP Cíclico/metabolismo , Endotélio Vascular/fisiologia , Expressão Gênica/efeitos dos fármacos , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
15.
Am J Physiol Endocrinol Metab ; 317(2): E350-E361, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211619

RESUMO

We proposed that circulating metabolites generated by the intestinal microbiota can affect vascular function. One such metabolite, indole 3-propionic acid (IPA), can activate the pregnane X receptor(PXR), a xenobiotic-activated nuclear receptor present in many tissues, including the vascular endothelium. We hypothesized that IPA could regulate vascular function by modulating PXR activity. To test this, Pxr+/+ mice were administered broad-spectrum antibiotics for 2 wk with IPA supplementation. Vascular function was evaluated by bioassay using aorta and pulmonary artery ring tissue from antibiotic-treated Pxr+/+ and Pxr-/-mice, supplemented with IPA, and using aorta tissue maintained in organ culture for 24 h in the presence of IPA. Endothelium-dependent, nitric oxide(NO)-mediated muscarinic and proteinase-activated receptor 2(PAR2)-stimulated vasodilation was assessed. Endothelial nitric oxide synthase (eNOS) abundance was evaluated in intact tissue or in aorta-derived endothelial cell cultures from Pxr+/+ and Pxr-/- mice, and vascular Pxr levels were assessed in tissues obtained from Pxr+/+ mice treated with antibiotics and supplemented with IPA. Antibiotic-treated Pxr+/+ mice exhibited enhanced agonist-induced endothelium-dependent vasodilation, which was phenocopied by tissues from either Pxr-/- or germ-free mice. IPA exposure reduced the vasodilatory responses in isolated and cultured vessels. No effects of IPA were observed for tissues obtained from Pxr-/- mice. Serum nitrate levels were increased in antibiotic-treated Pxr+/+and Pxr-/- mice. eNOS abundance was increased in aorta tissues and cultured endothelium from Pxr-/- mice. PXR stimulation reduced eNOS expression in cultured endothelial cells from Pxr+/+ but not Pxr-/- mice. The microbial metabolite IPA, via the PXR, plays a key role in regulating endothelial function. Furthermore, antibiotic treatment changes PXR-mediated vascular endothelial responsiveness by upregulating eNOS.


Assuntos
Células Endoteliais/efeitos dos fármacos , Indóis/farmacologia , Receptor de Pregnano X/agonistas , Receptor de Pregnano X/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Células Cultivadas , Células Endoteliais/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Indóis/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microbiota/efeitos dos fármacos , Microbiota/fisiologia , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Receptor de Pregnano X/genética , Vasodilatação/genética
16.
Environ Health Prev Med ; 24(1): 26, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043174

RESUMO

BACKGROUND: Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. METHODS: We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. RESULTS: High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. CONCLUSION: SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.


Assuntos
Plaquetas/metabolismo , Estatura/genética , Endotélio Vascular/fisiologia , Predisposição Genética para Doença , Hipertensão/sangue , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Contagem de Plaquetas
17.
Clin Appl Thromb Hemost ; 25: 1076029619851570, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31140290

RESUMO

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world and has a high risk of thromboembolism. The most effective approach, catheter ablation, requires evaluation by electrocardiography. The aim of our study was to investigate novel clinical markers that predict restoration of sinus rhythm (SR) after catheter ablation. Seventy-eight consecutive patients with AF underwent catheter ablation and were separated into 2 groups: restored SR and recurrent AF. The levels of 4 blood proteins (serum or plasma) and 3 mature microRNAs (miRNAs) and their primary miRNAs (pri-miRNAs) in serum were measured before and after ablation, and the associations between each parameter were analyzed statistically. Soluble thrombomodulin (s-TM) and plasminogen activator inhibitor-1 (PAI-1) levels increased above baseline after ablation in both the restored SR (s-TM 11.55 [2.92] vs 13.75 [3.38], P < .001; PAI-1 25.74 [15.25] vs 37.79 [19.56], P < .001) and recurrent AF (s-TM 10.28 [2.78] vs 11.67 [3.37], P < .001; PAI-1 26.16 [15.70] vs 40.74 [22.55], P < .001) groups. Levels of C-reactive protein and asymmetric dimethylarginine were not significantly changed. Pri-miR-126 levels significantly decreased after ablation in the recurrent AF group, but the other miRNAs and pri-miRNAs did not. The measurement of s-TM and pri-miR-126 in blood was a useful tool to reflect the condition of AF patients with catheter ablation.


Assuntos
Fibrilação Atrial/sangue , Fibrilação Atrial/terapia , Proteínas Sanguíneas/análise , Ablação por Cateter , MicroRNA Circulante/sangue , Endotélio Vascular/fisiologia , Idoso , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Taquicardia Sinusal/diagnóstico , Trombomodulina/sangue
18.
Physiol Rev ; 99(3): 1467-1525, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31140373

RESUMO

A central function of the vascular endothelium is to serve as a barrier between the blood and the surrounding tissue of the body. At the same time, solutes and cells have to pass the endothelium to leave or to enter the bloodstream to maintain homeostasis. Under pathological conditions, for example, inflammation, permeability for fluid and cells is largely increased in the affected area, thereby facilitating host defense. To appropriately function as a regulated permeability filter, the endothelium uses various mechanisms to allow solutes and cells to pass the endothelial layer. These include transcellular and paracellular pathways of which the latter requires remodeling of intercellular junctions for its regulation. This review provides an overview on endothelial barrier regulation and focuses on the endothelial signaling mechanisms controlling the opening and closing of paracellular pathways for solutes and cells such as leukocytes and metastasizing tumor cells.


Assuntos
Células Endoteliais/fisiologia , Endotélio Vascular/fisiologia , Transdução de Sinais/fisiologia , Animais , Barreira Alveolocapilar/fisiologia , Barreira Hematoencefálica/fisiologia , Endotélio Vascular/citologia , Humanos
19.
Arterioscler Thromb Vasc Biol ; 39(6): 1203-1211, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31070470

RESUMO

Objective- Adverse cardiovascular events occur more frequently in the morning than at other times of the day. Vascular endothelial function (VEF)-a robust cardiovascular risk marker-is impaired during this morning period. We recently discovered that this morning impairment in VEF is not caused by either overnight sleep or the inactivity that accompanies sleep. We determined whether the endogenous circadian system is responsible for this morning impairment in VEF. We also assessed whether the circadian system affects mechanistic biomarkers, that is, oxidative stress (malondialdehyde adducts), endothelin-1, blood pressure, and heart rate. Approach and Results- Twenty-one (11 women) middle-aged healthy participants completed a 5-day laboratory protocol in dim light where all behaviors, including sleep and activity, and all physiological measurements were evenly distributed across the 24-hour period. After baseline testing, participants underwent 10 recurring 5-hour 20-minute behavioral cycles of 2-hour 40-minute sleep opportunities and 2 hours and 40 minutes of standardized waking episodes. VEF, blood pressure, and heart rate were measured, and venous blood was sampled immediately after awakening during each wake episode. Independent of behaviors, VEF was significantly attenuated during the subjective night and across the morning ( P=0.04). Malondialdehyde adducts and endothelin-1 exhibited circadian rhythms with increases across the morning vulnerable period and peaks around noon ( P≤0.01). Both systolic ( P=0.005) and diastolic blood pressure ( P=0.04) were rhythmic with peaks in the late afternoon. Conclusions- The endogenous circadian system impairs VEF and increases malondialdehyde adducts and endothelin-1 in the morning vulnerable hours and may increase the risk of morning adverse cardiovascular events in susceptible individuals. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02202811.


Assuntos
Envelhecimento , Artéria Braquial/fisiologia , Ritmo Circadiano , Endotélio Vascular/fisiologia , Vasoconstrição , Vasodilatação , Adulto , Fatores Etários , Biomarcadores/sangue , Pressão Sanguínea , Artéria Braquial/metabolismo , Endotelina-1/sangue , Endotélio Vascular/metabolismo , Feminino , Frequência Cardíaca , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo , Fatores de Tempo
20.
Eur J Appl Physiol ; 119(7): 1663-1669, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055679

RESUMO

PURPOSE: Resistance exercise impairs endothelial function acutely. Therefore, it becomes important to devise an effective strategy for preventing acute endothelial dysfunction after resistance exercise. Herein, we tested the hypothesis that resistance exercise-induced temporal endothelial dysfunction is prevented by prior cycling. METHODS: Twelve young healthy subjects completed two randomized experimental trials: (1) resistance exercise only trial (RE trial), (2) resistance exercise with prior cycling trial (C + RE trial). Following baseline brachial artery flow-mediated dilation (FMD), the subjects maintained the supine position for 45 min in the RE trial; the subjects performed a 45 min of cycling (67.0 ± 1.7% HRmax) in the C + RE trial. After 45 min of resting or cycling, the subjects performed resistance exercise (69.7 ± 4.0 kg) at the same time points. Following the resistance exercise, they were asked to rest in the supine position for 60 min. Then FMD were repeated at 10, 30 and 60 min after the resistance exercise in both trials. RESULTS: The increased blood flow and shear rate after resistance exercise did not differ between trials, and these changes disappeared following resting in the supine position for 60 min. There was no significant interaction in %FMD responses. Both trials caused impairment in %FMD after the resistance exercise, and statistical significance was observed at 30 and 60 min after resistance exercise in the RE trial. CONCLUSION: The present study revealed that cycling for 45 min prior to resistance exercise was not sufficient to prevent the acute endothelial dysfunction after resistance exercise.


Assuntos
Endotélio Vascular/fisiologia , Treinamento de Resistência/efeitos adversos , Vasodilatação , Pressão Sanguínea , Artéria Braquial/fisiologia , Humanos , Masculino , Distribuição Aleatória , Fluxo Sanguíneo Regional , Adulto Jovem
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