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1.
Arterioscler Thromb Vasc Biol ; 41(3): 999-1011, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33441027

RESUMO

Platelets rapidly undergo responsive transitions in form and function to repair vascular endothelium and mediate hemostasis. In contrast, heterogeneous platelet subpopulations with a range of primed or refractory phenotypes gradually arise in chronic inflammatory and other conditions in a manner that may indicate or support disease. Qualitatively distinguishable platelet phenotypes are increasingly associated with a variety of physiological and pathological circumstances; however, the origins and significance of platelet phenotypic variation remain unclear and conceptually vague. As changes in platelet function in disease exhibit many similarities to platelets following the activation of platelet agonist receptors, the intracellular responses of platelets common to hemostasis and inflammation may provide insights to the molecular basis of platelet phenotype. Here, we review concepts around how protein-level relations-from platelet receptors through intracellular signaling events-may help to define platelet phenotypes in inflammation, immune responses, aging, and other conditions. We further discuss how representing systems-wide platelet proteomics data profiles as circuit-like networks of causally related intracellular events, or, pathway maps, may inform molecular definitions of platelet phenotype. In addition to offering insights into platelets as druggable targets, maps of causally arranged intracellular relations underlying platelet function can also advance precision and interceptive medicine efforts by leveraging platelets as accessible, dynamic, endogenous, circulating biomarkers of vascular wellness and disease. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Plaquetas/fisiologia , Proteoma/fisiologia , Doenças Vasculares/sangue , Animais , Biomarcadores/sangue , Endotélio Vascular/fisiologia , Hemostasia/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Modelos Cardiovasculares , Fenótipo , Proteômica , Transdução de Sinais , Doenças Vasculares/fisiopatologia
3.
J Sports Med Phys Fitness ; 60(8): 1159-1166, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32955842

RESUMO

BACKGROUND: Endothelial function assessment may provide important insights into the cardiovascular function and long-term effects of exercise training. Many studies have investigated the possible negative effects on cardiovascular function due to extreme athletic performance, leading to undesirable effects. The purposes of this study were to investigate the acute effects of maximal intensity exercise on endothelium-dependent vasodilation, and to understand the patterns of flow-mediated dilation (FMD) change following maximal exercise in elite female athletes with a high-volume training history. METHODS: Twenty-six elite female soccer players (mean age, 22±4 years; BMI, 21±2 kg/m2; VO2max, 41±4 mL/kg/min) were evaluated. Brachial artery FMD was determined using high-resolution ultrasound at rest, and after 15 and 60 min of maximal cardiopulmonary exercise (CPX) testing on a treadmill. Flow velocity was measured at baseline and during reactive hyperemia at the same periods. RESULTS: Rest FMD was 12.4±5.5%. Peak diameter in response to reactive hyperemia was augmented after 15 min of CPX (3.5±0.4 vs. 3.6±0.4 mm, P<0.05), returning to resting values after 60 min. However, %FMD did not change among time periods. There were two characteristic patterns of FMD response following CPX. Compared to FMD at rest, half of the subjects responded with an increased FMD following maximum exercise (10.5±6.1 vs. 17.8±7.5%, P<0.05). The other subjects demonstrated a reduced FMD response following maximum exercise (14.2±4.3 vs. 10.9±3.2%, P<0.01). CONCLUSIONS: These results indicate that elite female soccer players presented robust brachial artery FMD at rest, with a heterogeneous FMD response to acute exercise with a 50% FMD improvement rate.


Assuntos
Endotélio Vascular/fisiologia , Exercício Físico/fisiologia , Condicionamento Físico Humano/fisiologia , Futebol/fisiologia , Vasodilatação/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiologia , Teste de Esforço , Feminino , Humanos , Fluxo Sanguíneo Regional/fisiologia , Adulto Jovem
4.
Life Sci ; 259: 118377, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898526

RESUMO

The endothelium is the innermost vascular lining performing significant roles all over the human body while maintaining the blood pressure at physiological levels. Malfunction of endothelium is thus recognized as a biomarker linked with many vascular diseases including but not limited to atherosclerosis, hypertension and thrombosis. Alternatively, prevention of endothelial malfunctioning or regulating the functions of its associated physiological partners like endothelial nitric oxide synthase can prevent the associated vascular disorders which account for the highest death toll worldwide. While many anti-hypertensive drugs are available commercially, a comprehensive description of the key physiological roles of the endothelium and its regulation by endothelial nitric oxide synthase or vice versa is the need of the hour to understand its contribution in vascular homeostasis. This, in turn, will help in designing new therapeutics targeting endothelial nitric oxide synthase or its interacting partners present in the cellular pool. This review describes the central role of vascular endothelium in the regulation of endothelial nitric oxide synthase while outlining the emerging drug targets present in the vasculature with potential to treat vascular disorders including hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Endotélio Vascular/fisiologia , Coração/fisiologia , Óxido Nítrico Sintase Tipo III/metabolismo , Animais , Endotélio Vascular/metabolismo , Humanos
5.
Med Hypotheses ; 143: 110142, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32759013

RESUMO

BACKGROUND: Pulmonary hypertension is a significant complication for some patients with COVID-19 pneumonia, especially those requiring intensive care. Tachyphylaxis to the current therapy, inhaled nitric oxide (iNO), is also common. In vitro, folic acid directly increases nitric oxide (NO) production and extends its duration of action; effects which could be of benefit in reversing pulmonary hypertension and severe hypoxaemia. Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). HYPOTHESIS: A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion. We therefore hypothesise that folic acid, 5 mg or greater, is a useful therapeutic option for pulmonary hypertension and/or refractory severe hypoxaemia, in patients with severe COVID-19 associated pneumonia in whom NO therapy is considered, with a very low risk of adverse effects.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Ácido Fólico/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/metabolismo , Pandemias , Pneumonia Viral/complicações , Administração por Inalação , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Ativação Enzimática/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Humanos , Hipertensão Pulmonar/complicações , Hipóxia/tratamento farmacológico , Hipóxia/etiologia , Camundongos , Óxido Nítrico/administração & dosagem , Óxido Nítrico/uso terapêutico , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Taquifilaxia
6.
Am J Respir Cell Mol Biol ; 63(4): 531-539, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32663411

RESUMO

Caveolae are prominent plasmalemmal invaginations in endothelial cells, especially in the lung vasculature, which comprises a vast surface area. PV1 (plasmalemmal vesicle-associated protein-1), a 60-kD glycoprotein expressed in endothelial cells, is essential for generating spoke-like diaphragmatic structures that span the neck region of endothelial caveolae. However, their role in caveolae-mediated uptake and endothelial-barrier function is unknown. Here, we generated mice with endothelial cell-specific deletion of PV1 through tamoxifen-induced Cdh5.Cre.ERT2 (endothelial-specific vascular cadherin.Cre.estrogen receptor 2)-mediated excision of the floxed PV1 allele. We observed that loss of PV1 specifically in endothelial cells increased lung vascular permeability of fluid and protein, indicating that PV1 is required for maintenance of lung vascular-barrier integrity. Endothelial-specific PV1 deletion also increased caveolae-mediated uptake of tracer albumin compared with controls, promoted Au-albumin accumulation in the bulb of caveolae, and induced caveolar swelling. In addition, we observed the progressive loss of plasma proteins from the circulation and reduced arterial pressure resulting from transudation of water and protein as well as edema formation in multiple tissues, including lungs. These changes seen after endothelial-specific PV1 deletion occurred in the absence of disruption of endothelial junctions. We demonstrated that exposure of wild-type mice to endotoxin, which is known to cause acute lung injury and increase protein permeability, also significantly reduced PV1 protein expression. We conclude that the key function of PV1 is to regulate lung endothelial permeability through its ability to restrict the entry of plasma proteins such as albumin into caveolae and their transport through the endothelial barrier.


Assuntos
Permeabilidade Capilar/fisiologia , Cavéolas/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Pulmão/metabolismo , Proteínas de Membrana/metabolismo , Albuminas/metabolismo , Animais , Endotélio Vascular/fisiologia , Pulmão/fisiologia , Camundongos , Camundongos Endogâmicos C57BL
7.
Medicine (Baltimore) ; 99(27): e21062, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629734

RESUMO

BACKGROUND: The benefits of high-intensity interval training (HIIT) are well-known, there is insufficient evidence about the effects of HIIT on heart failure with preserved ejection fraction (HFpEF). METHOD: Multiple databases include MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, PEDro, Cochrane Library, and Google Scholar are used to search for randomized controlled trials investigating the effects of HIIT on HFpEF. All related articles published with the English language with no time limitation will be included. Two reviews independently conducted the selection, data extraction, and quality assessment. The primary outcome is exercise capacity. The secondary outcomes include quality of life (QoL), blood pressure (BP), ventricular function, and left ventricular diastolic function, symptom improvement, endothelial function, and arterial stiffness. Data analysis is performed with Review Manager Software (Version 5.3). RESULT: This systematic review and meta-analysis aim to evaluate the efficacy of HIIT on HFpEF, its outcome will provide reliable evidence for future studies. CONCLUSION: The findings of this study will be published in a related peer-reviewed journal. REGISTRATION NUMBER: INPLASY202050097.


Assuntos
Insuficiência Cardíaca/reabilitação , Treinamento Intervalado de Alta Intensidade/métodos , Volume Sistólico/fisiologia , Pressão Sanguínea/fisiologia , Diástole/fisiologia , Endotélio Vascular/fisiologia , Estudos de Avaliação como Assunto , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/psicologia , Humanos , Qualidade de Vida/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rigidez Vascular/fisiologia , Função Ventricular Esquerda/fisiologia
8.
PLoS One ; 15(7): e0235604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645079

RESUMO

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response (SIRS) and affects the organ vascular bed. Experimentally, the lack of pulsatility alters myogenic tone of resistance arteries and increases the parietal inflammatory response. The purpose of this study was to compare the vascular reactivity of the internal thoracic arteries (ITAs) due to the inflammatory response between patients undergoing coronary artery bypass grafting (CABG) under CPB with a roller pump or with a centrifugal pump. METHODS: Eighty elective male patients undergoing CABG were selected using one or two internal thoracic arteries under CPB with a roller pump (RP group) or centrifugal pump (CFP group). ITA samples were collected before starting CPB (Time 1) and before the last coronary anastomosis during aortic cross clamping (Time 2). The primary endpoint was the endothelium-dependent relaxation of ITAs investigated using wire-myography. The secondary endpoint was the parietal inflammatory response of arteries defined by the measurements of superoxide levels, leukocytes and lymphocytes rate and gene expression of inflammatory proteins using. Terminal complement complex activation (SC5b-9) and neutrophil activation (elastase) analysis were performed on arterial blood at the same times. RESULTS: Exposure time of ITAs to the pump flow was respectively 43.3 minutes in the RP group and 45.7 minutes in the CFP group. Acetylcholine-dependent relaxation was conserved in the two groups whatever the time. Gene expression of C3 and C4a in the artery wall decreased from Time 1 to Time 2. No oxidative stress was observed in the graft. There was no difference between the groups concerning the leukocytes and lymphocytes rate. SC5b-9 and elastase increased between Time 1 and Time 2. CONCLUSION: Endothelium-dependent relaxation of the internal thoracic arteries was preserved during CPB whatever the type of pump used. The inflammatory response observed in the blood was not found in the graft wall within this time frame. TRIAL REGISTRATION: Name of trial study protocol: IPITA Registration number (ClinicalTrials.gov): NCT04168853.


Assuntos
Ponte Cardiopulmonar/instrumentação , Ponte de Artéria Coronária/métodos , Coração Auxiliar/efeitos adversos , Artéria Torácica Interna/cirurgia , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/instrumentação , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Feminino , Humanos , Elastase de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Complicações Pós-Operatórias/epidemiologia , Transplantes/fisiologia , Transplantes/cirurgia , Vasoconstrição , Vasodilatação
9.
Proc Natl Acad Sci U S A ; 117(28): 16127-16137, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601214

RESUMO

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.


Assuntos
Adesivos/química , Materiais Revestidos Biocompatíveis/química , Peptídeos/química , Stents , Adesivos/síntese química , Animais , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Adesão Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Química Click , Células Progenitoras Endoteliais/citologia , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Miócitos de Músculo Liso/citologia , Óxido Nítrico/química , Compostos Organosselênicos/química , Peptídeos/síntese química , Proteínas/química , Coelhos , Stents/efeitos adversos , Trombose/etiologia , Trombose/prevenção & controle
10.
Nat Commun ; 11(1): 3653, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694534

RESUMO

The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer.


Assuntos
Mitocôndrias/metabolismo , Neoplasias/patologia , Neovascularização Patológica/patologia , Neovascularização Fisiológica , Cicatrização/fisiologia , Trifosfato de Adenosina/metabolismo , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Animais , Linhagem Celular Tumoral/transplante , Respiração Celular , Modelos Animais de Doenças , Embrião de Mamíferos , Desenvolvimento Embrionário/fisiologia , Células Endoteliais/fisiologia , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Feminino , Técnicas de Inativação de Genes , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Mitocôndrias/genética , Neoplasias/irrigação sanguínea , Fosforilação Oxidativa
11.
Artigo em Inglês | MEDLINE | ID: mdl-32708408

RESUMO

The current pool of data investigating the effects of a single resistance exercise session on endothelial function is divergent and inconclusive. Therefore, the purpose of the present study was to evaluate the effect of a single resistance exercise session on flow-mediated dilation (FMD) in trained individuals. Eleven healthy, young, recreationally resistance-trained individuals participated in the study. After determining the resistance exercise workload, the participants performed three sets of 10-12 repetition of leg press and leg extension exercises. By using ultrasound equipment, brachial artery FMD was assessed before (PRE) and 30 min after (POST) the resistance exercise protocol or resting (control) to evaluate endothelial function. A significant reduction in FMD response (PRE: 5.73% ± 1.21% vs. POST: 4.03% ± 1.94%, p < 0.01) after resistance exercise was observed, accompanied by a large effect size (d = 1.05). No significant difference was observed in FMD in the control condition (PRE: 5.82% ± 1.19% vs. POST: 5.66% ± 1.24%, p = 0.704). Additionally, no significant difference in baseline brachial artery diameter between resistance exercise (PRE: 3.30 ± 0.32 vs. POST: 3.40 ± 0.34 mm, p = 0.494) and resting (PRE: 3.64 ± 0.41 vs. POST: 3.67 ± 0.62 mm, p = 0.825) was observed. Our findings showed that a single resistance exercise session induced a reduction in FMD in resistance-trained individuals.


Assuntos
Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiologia , Endotélio Vascular/fisiologia , Exercício Físico/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Treinamento de Resistência , Vasodilatação/fisiologia , Adulto , Dilatação , Endotélio Vascular/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Humanos , Masculino , Ultrassonografia , Adulto Jovem
12.
Int J Sports Med ; 41(11): 759-765, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32492734

RESUMO

A combination of yoga and blood flow restriction, each of which elicits marked pressor responses, may further increase blood pressure and myocardial oxygen demand. To determine the impact of a combination of yoga and blood flow restriction on hemodynamic responses, twenty young healthy participants performed 20 yoga poses with/without blood flow restriction bands placed on both legs. At baseline, there were no significant differences in any of the variables between the blood flow restriction and non-blood flow restriction conditions. Blood pressure and heart rate increased in response to the various yoga poses (p<0.01) but were not different between the blood flow restriction and non-blood flow restriction conditions. Rate-pressure products, an index of myocardial oxygen demand, increased significantly during yoga exercises with no significant differences between the two conditions. Rating of perceived exertion was not different between the conditions. Blood lactate concentration was significantly greater after performing yoga with blood flow restriction bands (p=0.007). Cardio-ankle vascular index, an index of arterial stiffness, decreased similarly after yoga exercise in both conditions while flow-mediated dilation remained unchanged. In conclusion, the use of lower body blood flow restriction bands in combination with yoga did not result in additive or synergistic hemodynamic and pressor responses.


Assuntos
Pressão Sanguínea , Hemodinâmica , Condicionamento Físico Humano/métodos , Fluxo Sanguíneo Regional , Coxa da Perna/irrigação sanguínea , Ioga , Adolescente , Adulto , Estudos Cross-Over , Endotélio Vascular/fisiologia , Feminino , Frequência Cardíaca , Humanos , Ácido Láctico/sangue , Masculino , Miocárdio/metabolismo , Consumo de Oxigênio , Percepção/fisiologia , Condicionamento Físico Humano/fisiologia , Esforço Físico/fisiologia , Rigidez Vascular , Vasodilatação , Adulto Jovem
13.
Exerc Sport Sci Rev ; 48(3): 133-139, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568925

RESUMO

Age-associated reduction in endothelial nitric oxide (NO) synthesis contributes to the development of cardiovascular diseases and sarcopenia. L-Citrulline is a precursor of NO with the ability to improve vascular function and muscle protein synthesis. We hypothesize that vascular and muscular benefits associated with oral L-citrulline supplementation might be augmented by concomitant supplementation with exercise training in older adults.


Assuntos
Envelhecimento/fisiologia , Citrulina/administração & dosagem , Suplementos Nutricionais , Exercício Físico/fisiologia , Condicionamento Físico Humano/fisiologia , Arginina/sangue , Disponibilidade Biológica , Índice de Massa Corporal , Endotélio Vascular/fisiologia , Endotélio Vascular/fisiopatologia , Humanos , Proteínas Musculares/biossíntese , Força Muscular , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Óxido Nítrico/biossíntese , Consumo de Oxigênio
14.
Life Sci ; 256: 117986, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32585245

RESUMO

AIMS: HSP70, a molecular chaperone, helps to maintain proteostasis. In muscle biology, however, evidence suggests HSP70 to have a more versatile range of functions, as genetic deletion of its inducible genes impairs Ca2+ handling, and consequently, cardiac and skeletal muscle contractility. Still, it is unknown whether HSP70 is involved in vascular reactivity, an intrinsic physiological mechanism of blood vessels. Therefore, we designed this study to test the hypothesis that proper vascular reactivity requires the assistance of HSP70. MAIN METHODS: We performed functional studies in a wire-myograph using thoracic aorta isolated from male Sprague Dawley rats. Experiments were conducted with and without an HSP70 inhibitor as well as in heat-stressed vessels. The expression levels of HSP70 were evaluated with Western blotting. NO and ROS levels were assessed with fluorescence microscopy. KEY FINDINGS: We report that blockade of HSP70 weakens contraction in response to phenylephrine (dose-response) in the aorta. Additionally, we demonstrated that inhibition of HSP70 affects the amplitude of the fast and of the slow components of the time-force curve. Corroborating these findings, we found that inhibition of HSP70, in vessels over-expressing this protein, partly rescues the contractile phenotype of aortic rings. Furthermore, we show that blockade of HSP70 facilitates relaxation in response to acetylcholine and clonidine without affecting the basal levels of NO and ROS. SIGNIFICANCE: Our work introduces an additional physiological role for HSP70, the assistance of vascular reactivity, which highlights this protein as a new player in vascular physiology, and therefore, uncovers a promising research avenue for vascular diseases.


Assuntos
Aorta Torácica/fisiologia , Endotélio Vascular/fisiologia , Proteínas de Choque Térmico HSP70/fisiologia , Músculo Liso Vascular/fisiologia , Acetilcolina/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/agonistas , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Fenilefrina/farmacologia , Nucleosídeos de Purina/farmacologia , Ratos , Ratos Sprague-Dawley , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
15.
Am J Physiol Regul Integr Comp Physiol ; 318(6): R1091-R1102, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32349514

RESUMO

In women who conceived with or without assisted reproduction, we evaluated endothelial function by EndoPAT [reactive hyperemia index (RHI)], circulating numbers of endothelial cells (CEC) and endothelial progenitor cells (EPC), and their function before during and after pregnancy. In vitro fertilization (IVF) pregnancies were stratified by method of conception and corpus luteum (CL) number-controlled ovarian stimulation (>1 CL) or programmed (0 CL) cycles and spontaneous singleton pregnancies (1 CL). We observed 1) comparable gestational decline of RHI in the three participant groups secondary to gestational rise of baseline preocclusion pulse-wave amplitude (PWA) incorporated into the RHI calculation by EndoPAT software; 2) progressive rise in "normalized" RHI throughout pregnancy (calculated by substituting prepregnancy baseline preocclusion PWA into the RHI equation), greater in spontaneous conception vs. IVF cohorts; 3) similar gestational increase of maximum PWA and time to maximum PWA after the ischemia stimulus among the three participant groups; 4) modest gestational increase of ischemia response (reactive hyperemia) in the spontaneous conception group and no change or significant decline, respectively, in women who conceived using programmed or controlled ovarian stimulation cycles; 5) enhanced basal nitric oxide production by early (primitive) outgrowth EPC during pregnancy in women who conceived spontaneously, but not through IVF; and 6) gestational increase in CEC in all three participant cohorts, more pronounced in women who conceived by IVF using programmed cycles. On balance, the evidence supported enhanced endothelial function during pregnancy in spontaneous conceptions but less so in IVF pregnancies using either controlled ovarian stimulation or programmed cycles.


Assuntos
Células Progenitoras Endoteliais/fisiologia , Endotélio Vascular/fisiologia , Fertilização In Vitro , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
16.
Am J Physiol Regul Integr Comp Physiol ; 319(1): R11-R18, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401628

RESUMO

Consumption of a single, sugar-sweetened beverage (SSB) impairs vascular endothelial function. Regular aerobic exercise improves endothelium-dependent vasodilation; however, it is unknown whether these beneficial effects persist with frequent SSB consumption. Therefore, the purpose of this study was twofold; we studied the effects of repetitive SSB consumption (75 g d-glucose, 3 times/day) for 1 wk (Glu, n = 13, 23 ± 4 yr, 23.5 ± 3.4 kg/m2) on endothelium-dependent vasodilation (FMD). Then, in a separate cohort, we investigated whether 45 min of moderate-intensity aerobic exercise on five separate days offset the hypothesized decrease in FMD during the Glu protocol (Glu+Ex, n = 11, 21 ± 3 yr, 23.8 ± 2.4 kg/m2). Baseline, fasting [glucose] (P = 0.15), [insulin] (P = 0.25), %FMD (P = 0.48), absolute FMD (P = 0.66), and shear rate area under the curve (SRAUC; P = 0.82) were similar between groups. Following the interventions, fasting [glucose] (Glu: 94 ± 6 to 92 ± 6 mg/dL, Glu+Ex: 89 ± 8 to 87 ± 6 mg/dL, P = 0.74) and [insulin] (Glu: 11.3 ± 6.2 to 11.8 ± 8.9 µU/mL, Glu+Ex: 8.7 ± 2.9 to 9.4 ± 3.2 µU/mL, P = 0.89) were unchanged. %FMD was reduced in Glu (6.1 ± 2.2 to 5.1 ± 1.3%) and increased in Glu+Ex (6.6 ± 2.2 to 7.8 ± 2.4%, P < 0.05 for both). SRAUC increased similarly in both Glu [17,715 ± 8,275 to 22,922 ± 4,808 arbitrary units (A.U.)] and Glu+Ex (18,216 ± 4,516 to 21,666 ± 5,392 A.U., main effect of time P < 0.05). When %FMD was adjusted for SRAUC, attenuation was observed in Glu (0.41 ± 0.18 to 0.23 ± 0.08%/s × 103, P < 0.05) but not Glu+Ex (0.38 ± 0.14 to 0.38 ± 0.13%/s × 103, P = 0.88). Despite unchanged fasting [glucose] and [insulin], repeated consumption of SSBs impaired conduit artery vascular endothelial function. Additionally, subjects who engaged in regular moderate-intensity aerobic exercise did not demonstrate the same SSB-induced endothelial dysfunction. Collectively, these data suggest aerobic exercise may offset the deleterious effects of repetitive SSB consumption.


Assuntos
Endotélio Vascular/fisiologia , Exercício Físico/fisiologia , Bebidas Adoçadas com Açúcar/efeitos adversos , Adolescente , Adulto , Glicemia/análise , Estudos de Coortes , Dieta , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/fisiopatologia , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/fisiopatologia , Insulina/sangue , Masculino , Vasodilatação/efeitos dos fármacos , Adulto Jovem
17.
Am J Physiol Regul Integr Comp Physiol ; 319(1): R19-R25, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401629

RESUMO

Microvascular endothelial dysfunction, a precursor to atherosclerotic cardiovascular disease, increases with aging. Endothelium-derived hyperpolarizing factors (EDHFs), which act through K+ channels, regulate blood flow and are important to vascular health. It is unclear how EDHFs change with healthy aging. To evaluate microvascular endothelial reliance on K+ channel-mediated dilation as a function of age in healthy humans. Microvascular function was assessed using intradermal microdialysis in healthy younger (Y; n = 7; 3 M/4 W; 26 ± 1 yr) and older adults (O; n = 12; 5 M/7 W; 64 ± 2 yr) matched for V̇o2peak (Y: 39.0 ± 3.8, O: 37.6 ± 3.1 mL·kg-1·min-1). Participants underwent graded local infusions of: the K+ channel activator Na2S (10-6 to 10-1 M), acetylcholine (ACh, 10-10 to 10-1 M), ACh + the K+ channel inhibitor tetraethylammonium (TEA; 25 or 50 mM), and ACh + the nitric oxide synthase-inhibitor l-NAME (15 mM). Red blood cell flux was measured with laser-Doppler flowmetry and used to calculate cutaneous vascular conductance (CVC; flux/mean arterial pressure) as a percentage of each site-specific maximum (%CVCmax, 43°C+28 mM sodium nitroprusside). The %CVCmax response to Na2S was higher in older adults (mean, O: 51.7 ± 3.9% vs. Y: 36.1 ± 5.3%; P = 0.03). %CVCmax was lower in the ACh+TEA vs. the ACh site starting at 10-5 M (ACh: 34.0 ± 5.7% vs. ACh+TEA: 19.4 ± 4.5%; P = 0.002) in older and at 10-4 M (ACh: 54.5 ± 9.4% vs. ACh+TEA: 31.2 ± 6.7%; P = 0.0002) in younger adults. %CVCmax was lower in the ACh+l-NAME vs. the ACh site in both groups starting at 10-4 M ACh (Y: P < 0.001; O: P = 0.02). Healthy active older adults have enhanced K+ channel-dependent endothelial vasodilatory mechanisms, suggesting increased responsiveness to EDHFs with age.


Assuntos
Endotélio Vascular/fisiologia , Envelhecimento Saudável/fisiologia , Canais de Potássio/fisiologia , Vasodilatação/fisiologia , Adulto , Idoso , Envelhecimento/fisiologia , Limiar Anaeróbio/fisiologia , Fatores Biológicos/fisiologia , Inibidores Enzimáticos/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , NG-Nitroarginina Metil Éster/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/agonistas , Fluxo Sanguíneo Regional/fisiologia
18.
Am J Physiol Heart Circ Physiol ; 319(1): H123-H132, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32469638

RESUMO

Cold exposure causes cutaneous vasoconstriction via a reflex increase in sympathetic activity and a local effect to augment adrenergic constriction. Local cooling also initiates cutaneous dilatation, which may function to restrain cold-induced constriction. However, the underlying mechanisms and physiological role of cold-induced dilatation have not been defined. Experiments were performed to assess the role of endothelial-derived mediators in this response. In isolated pressurized cutaneous mouse tail arteries, cooling (28°C) did not affect the magnitude of dilatation to acetylcholine in preconstricted arteries. However, inhibition of nitric oxide (NO) [NG-nitro-l-arginine methyl ester (l-NAME)] and prostacyclin (PGI2) (indomethacin) reduced acetylcholine-induced dilatation at 37°C but not at 28°C, suggesting that cooling increased NO/PGI2-independent dilatation. This NO/PGI2-independent dilatation was reduced by inhibition of endothelial SK (UCL1684) and IK (TRAM34) Ca2+-activated K+-channels (KCa), consistent with endothelium-derived hyperpolarization (EDH). Cooling also increased dilatation to direct activation of KCa channels (SKA31, CyPPA) but did not affect dilatation to exogenous NO (DEA-NONOate). This cooling-induced increase in EDH-type dilatations was associated with divergent effects on potential downstream EDH mechanisms: cooling reduced dilatation to K+, which mimics an intercellular K+ cloud, but increased direct communication between endothelial and smooth muscle cells (myoendothelial coupling), assessed by cellular transfer of biocytin. Indeed, inhibition of gap junctions (carbenoxolone) abolished the EDH-type component of dilatation to acetylcholine during cooling but did affect NO-dominated dilatation at 37°C. Cooling also inhibited U46619 constriction that was prevented by inhibition of IK and SK KCa channels or inhibition of gap junctions. The results suggest that cooling dilates cutaneous arteries by increasing myoendothelial communication and amplifying EDH-type dilatation.NEW & NOTEWORTHY Cold causes cutaneous vasoconstriction to restrict heat loss. Although cold also initiates cutaneous dilatation, the mechanisms and role of this dilatation have not been clearly defined. This study demonstrates that cooling increases myoendothelial coupling between smooth muscle and endothelial cells in cutaneous arteries, which is associated with increased endothelium-derived hyperpolarization (EDH)-type dilatation. Dysfunction in this process may contribute to excessive cold-induced constriction and tissue injury.


Assuntos
Artérias/fisiologia , Temperatura Baixa , Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiologia , Pele/irrigação sanguínea , Vasodilatação , Acetilcolina/farmacologia , Alcanos/farmacologia , Animais , Artérias/efeitos dos fármacos , Carbenoxolona/farmacologia , Endotélio Vascular/metabolismo , Epoprostenol/farmacologia , Indometacina/farmacologia , Masculino , Potenciais da Membrana , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Canais de Potássio Cálcio-Ativados/metabolismo , Pirazóis/farmacologia , Compostos de Quinolínio/farmacologia , Vasoconstrição , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
19.
PLoS One ; 15(5): e0233484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470022

RESUMO

BACKGROUND: Measurement of the reactive hyperemia index (RHI) using peripheral arterial tonometry (PAT) has shown benefits in the evaluation of vascular endothelial function and prediction of cardiovascular disease prognosis. Thus, it is important to examine the factors that promote the RHI. In this study, we aimed to investigate the effect of molecular hydrogen (H2) on reactive hyperemia-PAT of the small arteries of fingers in healthy people. METHODS: To determine the efficacy of H2 for improving peripheral vascular endothelial function, water containing high H2 concentrations was administered to participants, and the Ln_RHI was measured in the finger vasculature. Sixty-eight volunteers were randomly divided into two groups: a placebo group (n = 34) that drank molecular nitrogen (N2)-containing water and a high H2 group (n = 34) that drank high H2 water (containing 7 ppm of H2: 3.5 mg H2 in 500-mL water). The Ln_RHI was measured before ingesting the placebo or high H2 water, 1 h and 24 h after the first ingestion, and 14 days after daily ingestion of high H2 water or the placebo. The mixed effects model for repeated measures was used in data analysis. RESULTS: The high H2 group had a significantly greater improvement in Ln_RHI than the placebo group. Ln_RHI improved by 22.2% (p<0.05) at 24 h after the first ingestion of high H2 water and by 25.4% (p<0.05) after the daily consumption of high H2 water for 2 weeks. CONCLUSIONS: Daily consumption of high H2 water improved the endothelial function of the arteries or arterioles assessed by the PAT test. The results suggest that the continuous consumption of high H2 water contributes to improved cardiovascular health.


Assuntos
Endotélio Vascular/fisiologia , Hidrogênio/administração & dosagem , Hiperemia/etiologia , Adulto , Fatores Biológicos/agonistas , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Feminino , Dedos/irrigação sanguínea , Voluntários Saudáveis , Humanos , Hiperemia/fisiopatologia , Masculino , Manometria/métodos , Pessoa de Meia-Idade , Modelos Cardiovasculares , Óxido Nítrico/agonistas , Óxido Nítrico/fisiologia , Fatores de Risco , Água/análise
20.
Am J Physiol Heart Circ Physiol ; 318(5): H1337-H1345, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32302493

RESUMO

Endothelial dysfunction is thought to underpin atherosclerotic cardiovascular disease. The most widely used in vivo test of endothelial function is flow-mediated dilation (FMD). However, the results of FMD may be subject to some confounding factors that are not fully understood. We investigated potential biophysical confounding factors that could cause a disassociation between FMD and true endothelial cell shear stress response (the release of endothelium-dependent relaxing factors in response to wall shear stress). Arterial hemodynamics during FMD was simulated using a novel computational modeling approach. The model included an endothelial response function relating changes in wall shear stress to changes in local vascular stiffness in the arm arteries and accounted for vascular stiffening with increasing blood pressure. The hemodynamic effects of cuff inflation and deflation were modeled by prescribing intraluminal arterial pressure changes and peripheral vasodilation. Evolution of arterial diameter and flow velocity during FMD was assessed by comparison against in vivo data. Our model revealed that vasoconstriction occurring immediately after cuff deflation is independent of endothelial response function and entirely caused by the change in transmural pressure along conduit arteries. Moreover, for the same endothelial response function model, FMD values increased exponentially with increasing peak flow velocity, decreased linearly with increasing arterial stiffness at a rate of 0.95%/MPa, and increased linearly with increasing central blood pressure at a rate of 0.22%/mmHg. Dependence of FMD on confounding factors, such as arterial stiffness and blood pressure, suggests that the current FMD test may not reflect the true endothelial cell response.NEW & NOTEWORTHY First, a novel computational model simulating arterial hemodynamics during flow-mediated dilation (FMD) was proposed. Second, the model was used to explain why FMD may be influenced by endothelium-independent factors, showing that FMD results are 1) partly masked by the vasoconstriction due to the change in transmural pressure and 2) affected by physiological factors (i.e., arterial stiffness and arterial blood pressure) that are difficult to eliminate due to their multiple interactions.


Assuntos
Pressão Sanguínea , Endotélio Vascular/fisiologia , Modelos Cardiovasculares , Vasodilatação , Adulto , Humanos , Masculino , Fluxo Sanguíneo Regional , Rigidez Vascular
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