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1.
Nihon Yakurigaku Zasshi ; 155(6): 395-400, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33132257

RESUMO

In normal condition, vasculature transports only small molecules such as nutrients across vascular wall. When inflammation occurs, inflammatory stimuli increase the permeability of vessel, which induces the extravasation of molecules larger than 40 kDa including plasma proteins. These extravasated molecules cause further inflammation by promoting the infiltration of inflammatory cells and the production of inflammatory mediators. Although it is known that vascular hyper-permeability plays an important role in inflammation, the detailed mechanism of vascular permeability regulation is still unclear. It is known that vascular permeability is controlled by two types of cells: endothelial cells and vascular mural cells. Endothelial cells cover the luminal side of vascular wall in a single layer and form endothelial barrier. Vascular mural cells regulate the blood flow volume of the downstream tissue by contracting or relaxing vascular wall. Endothelial barrier enhancement and vasocontraction suppress the vascular permeability, while endothelial barrier disruption and vasorelaxation promote it. Vascular permeability is regulated by the balance between the response of endothelial cells and vascular mural cells. Prostanoids are cell membrane-derived lipid mediators which bind to each specific G protein-coupled receptor (GPCR), prostanoid receptors. Recently, several studies showed that prostanoids regulate vascular permeability by acting on endothelial cells and/or vascular mural cells. In this review, we would like to describe the role of each prostanoid in vascular permeability by focusing on the characteristics of each specific receptor.


Assuntos
Permeabilidade Capilar , Prostaglandinas , Células Endoteliais , Endotélio Vascular/metabolismo , Prostaglandinas/metabolismo , Vasodilatação
2.
Wiad Lek ; 73(9 cz. 2): 1940-1943, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33148837

RESUMO

OBJECTIVE: The aim: Is to evaluate copetin's, MRproADM's and troponin's I dynamic in patients with acute myocardial infarction depending on the degree of concomitant obesity. PATIENTS AND METHODS: Material and methods: The study included 105 patients with AMI. There were formed 2 groups: 1st group of patients with AMI and concomitant obesity (n=75), 2nd group - patients with AMI without obesity (n=30). 37 patients had obesity of the I degree, 38 patients - II degree. The groups were comparable in age and gender. Copeptin, MRproADM, troponin I were determined by enzyme immunoassay method. Data are presented as mean values and the error of the mean (M±m). Differences were considered statistically significant at p<0,05. RESULTS: Results: It was found an increased copeptin's level by 73,8 % (p<0,001) in obesity I degree and by 205,9 % in obesity II degree compared with group with isolated AMI, MRproADM - by 30,68 % (p<0,001) and 54,5 % (p<0,001) respectively. Concentration of copeptin was higher by 76 % (p<0,001) in patients with AMI and II degree obesity comparing to patients with obesity of I degree, and MRproADM - by 18,3% (p<0,001) respectively. Troponin I value fully corresponded the comparison group both in obesity of I degree and II degree (p>0,05). CONCLUSION: Conclusions: The present study provides evidence that a high activity of copeptin and MRproADM in patients with AMI and obesity of I degree with an excessive activity of a marker of vasoconstriction copeptin in conditions of moderate inadequate to the needs MRproADM functioning in patients with obesity of II degree.


Assuntos
Infarto do Miocárdio , Troponina I , Biomarcadores , Glicopeptídeos , Humanos , Infarto do Miocárdio/complicações , Obesidade/complicações , Estudos Prospectivos , Vasoconstrição , Vasodilatação
3.
Vestn Oftalmol ; 136(5): 67-76, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33056966

RESUMO

PURPOSE: To study the reactivity of the vascular endothelium and the elastic properties of the upper and lower extremities, and assess the vascular innervation effect of Cytoflavin in patients with stable and rapidly progressive primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study included 67 patients with POAG (mean age 66.3±1.5 years), among them 31 with stable and 36 with rapidly progressive glaucoma. During the first stage of the study, the reactivity of the vascular endothelium was assessed with reactive hyperemia test; the viscoelastic properties of the upper and lower extremities were evaluated using volumetric sphygmomanometry. For the second stage of the study, patients were divided into the main group (n=20) that received intravenous injections of 10 ml Cytoflavin with 200 ml of 5% glucose solution for 10 days and then 2 tablets twice a day for 60 days, and the control group (n=16). RESULTS: The function of the vascular endothelium was significantly reduced in patients with rapidly progressive POAG. Correlation analysis revealed a negative correlation between the flow-dependent vasodilation (FDV), and the duration of POAG and initial diameter of the brachial artery (r=0.5, p<0.05 and r=0.6, p<0.05, respectively). Pathological response of vessel endothelium was detected in 88% of patients with stable and 96% of patients with rapidly progressive POAG. Cytoflavin was found to have positive effects on the endothelium in patients with POAG. CONCLUSION: The obtained data can be used for identification of risk factors for rapid POAG progression and optimization of its treatment.


Assuntos
Glaucoma de Ângulo Aberto , Idoso , Artéria Braquial , Endotélio Vascular , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Vasodilatação
4.
Rev Cardiovasc Med ; 21(3): 315-319, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070537

RESUMO

Great attention has been paid to endothelial dysfunction (ED) in coronavirus disease 2019 (COVID-19). There is growing evidence to suggest that the angiotensin converting enzyme 2 receptor (ACE2 receptor) is expressed on endothelial cells (ECs) in the lung, heart, kidney, and intestine, particularly in systemic vessels (small and large arteries, veins, venules, and capillaries). Upon viral infection of ECs by severe acute respiratory syndrome coronarvirus 2 (SARS-CoV-2), ECs become activated and dysfunctional. As a result of endothelial activation and ED, the levels of pro-inflammatory cytokines (interleukin -1, interleukin-6 (IL-6), and tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1), von Willebrand factor (vWF) antigen, vWF activity, and factor VIII are elevated. Higher levels of acute phase reactants (IL-6, C-reactive protein, and D-dimer) are also associated with SARS-CoV-2 infection. Therefore, it is reasonable to assume that ED contributes to COVID-19-associated vascular inflammation, particularly endotheliitis, in the lung, heart, and kidney, as well as COVID-19-associated coagulopathy, particularly pulmonary fibrinous microthrombi in the alveolar capillaries. Here we present an update on ED-relevant vasculopathy in COVID-19. Further research for ED in COVID-19 patients is warranted to understand therapeutic opportunities.


Assuntos
Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/complicações , Endotélio Vascular/fisiopatologia , Pneumonia Viral/complicações , Doenças Vasculares/etiologia , Vasodilatação/fisiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Infecções por Coronavirus/epidemiologia , Humanos , Inflamação/etiologia , Inflamação/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Doenças Vasculares/fisiopatologia
5.
Rev Cardiovasc Med ; 21(3): 339-344, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070539

RESUMO

There is emerging evidence to suggest that vitamin D deficiency is associated with adverse outcomes in COVID-19 patients. Conversely, vitamin D supplementation protects against an initial alveolar diffuse damage of COVID-19 becoming progressively worse. The mechanisms by which vitamin D deficiency exacerbates COVID-19 pneumonia remain poorly understood. In this review we describe the rationale of the putative role of endothelial dysfunction in this event. Herein, we will briefly review (1) anti-inflammatory and anti-thrombotic effects of vitamin D, (2) vitamin D receptor and vitamin D receptor ligand, (3) protective role of vitamin D against endothelial dysfunction, (4) risk of vitamin D deficiency, (5) vitamin D deficiency in association with endothelial dysfunction, (6) the characteristics of vitamin D relevant to COVID-19, (7) the role of vitamin D on innate and adaptive response, (8) biomarkers of endothelial cell activation contributing to cytokine storm, and (9) the bidirectional relationship between inflammation and homeostasis. Finally, we hypothesize that endothelial dysfunction relevant to vitamin D deficiency results from decreased binding of the vitamin D receptor with its ligand on the vascular endothelium and that it may be immune-mediated via increased interferon 1 α. A possible sequence of events may be described as (1) angiotensin II converting enzyme-related initial endothelial injury followed by vitamin D receptor-related endothelial dysfunction, (2) endothelial lesions deteriorating to endothelialitis, coagulopathy and thrombosis, and (3) vascular damage exacerbating pulmonary pathology and making patients with vitamin D deficiency vulnerable to death.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Endotélio Vascular/fisiopatologia , Pneumonia Viral/epidemiologia , Vasodilatação/fisiologia , Deficiência de Vitamina D/epidemiologia , Comorbidade , Infecções por Coronavirus/fisiopatologia , Humanos , Pandemias , Pneumonia Viral/fisiopatologia , Deficiência de Vitamina D/fisiopatologia
6.
Medicine (Baltimore) ; 99(41): e22318, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031270

RESUMO

INTRODUCTION: The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters," which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation.The aim of this study was to investigate 3 of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS). METHODS: This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6 and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30-male athletes between 18 and 40 years and will be compared with a placebo. On each of the 3 appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the 3 supplements once after a wash-out period of at least 1 week. Perfusion will be quantified via VueBox quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters. DISCUSSION: The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.


Assuntos
Arginina/administração & dosagem , Citrulina/administração & dosagem , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/diagnóstico por imagem , Chá , Ultrassonografia/métodos , Adolescente , Adulto , Meios de Contraste , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasodilatação
7.
BMC Pulm Med ; 20(1): 269, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066765

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects. METHODS: We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA). RESULTS: The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group. CONCLUSIONS: This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients.


Assuntos
Dióxido de Carbono/metabolismo , Infecções por Coronavirus/metabolismo , Eritrócitos/metabolismo , Hipóxia/metabolismo , Óxido Nítrico/metabolismo , Oxigênio/metabolismo , Pneumonia Viral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Betacoronavirus , Gasometria , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Feminino , Citometria de Fluxo , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pressão Parcial , Projetos Piloto , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/metabolismo , Vasodilatação , Adulto Jovem
8.
Nat Commun ; 11(1): 4883, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985528

RESUMO

Early stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement. Although speculated that such paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. Herein, a mathematical model demonstrates that the large amount of pulmonary venous admixture observed in patients with early COVID-19 can be reasonably explained by a combination of pulmonary embolism, ventilation-perfusion mismatching in the noninjured lung, and normal perfusion of the relatively small fraction of injured lung. Although underlying perfusion heterogeneity exacerbates existing shunt and ventilation-perfusion mismatch in the model, the reported hypoxemia severity in early COVID-19 patients is not replicated without either extensive perfusion defects, severe ventilation-perfusion mismatch, or hyperperfusion of nonoxygenated regions.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Hipóxia/etiologia , Hipóxia/fisiopatologia , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Modelos Biológicos , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Circulação Pulmonar/fisiologia , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Humanos , Hipóxia/terapia , Pneumopatias/terapia , Conceitos Matemáticos , Modelos Cardiovasculares , Oxigenoterapia , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Tempo , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Relação Ventilação-Perfusão/fisiologia
9.
PLoS One ; 15(9): e0238946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956397

RESUMO

BACKGROUND: The origin of low frequency cerebral hemodynamic fluctuations (CHF) in the resting state remains unknown. Breath-by breath O2-CO2 exchange ratio (bER) has been reported to correlate with the cerebrovascular response to brief breath hold challenge at the frequency range of 0.008-0.03Hz in healthy adults. bER is defined as the ratio of the change in the partial pressure of oxygen (ΔPO2) to that of carbon dioxide (ΔPCO2) between end inspiration and end expiration. In this study, we aimed to investigate the contribution of respiratory gas exchange (RGE) metrics (bER, ΔPO2 and ΔPCO2) to low frequency CHF during spontaneous breathing. METHODS: Twenty-two healthy adults were included. We used transcranial Doppler sonography to evaluate CHF by measuring the changes in cerebral blood flow velocity (ΔCBFv) in bilateral middle cerebral arteries. The regional CHF were mapped with blood oxygenation level dependent (ΔBOLD) signal changes using functional magnetic resonance imaging. Temporal features and frequency characteristics of RGE metrics during spontaneous breathing were examined, and the simultaneous measurements of RGE metrics and CHF (ΔCBFv and ΔBOLD) were studied for their correlation. RESULTS: We found that the time courses of ΔPO2 and ΔPCO2 were interdependent but not redundant. The oscillations of RGE metrics were coherent with resting state CHF at the frequency range of 0.008-0.03Hz. Both bER and ΔPO2 were superior to ΔPCO2 in association with CHF while CHF could correlate more strongly with bER than with ΔPO2 in some brain regions. Brain regions with the strongest coupling between bER and ΔBOLD overlapped with many areas of default mode network including precuneus and posterior cingulate. CONCLUSION: Although the physiological mechanisms underlying the strong correlation between bER and CHF are unclear, our findings suggest the contribution of bER to low frequency resting state CHF, providing a novel insight of brain-body interaction via CHF and oscillations of RGE metrics.


Assuntos
Circulação Cerebrovascular/fisiologia , Taxa Respiratória/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Encéfalo/fisiologia , Dióxido de Carbono/sangue , Feminino , Voluntários Saudáveis , Hemodinâmica/fisiologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Artéria Cerebral Média/fisiologia , Oxigênio/sangue , Pressão Parcial , Respiração , Descanso/fisiologia , Ultrassonografia Doppler Transcraniana/métodos , Vasodilatação/fisiologia
10.
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
11.
PLoS One ; 15(9): e0239039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915892

RESUMO

BACKGROUND: Beta-blockers are often not the preferred treatment for patients with vasospastic angina. However, nebivolol, beta-blocker with nitric oxide-releasing effect, could theoretically improve coronary vasospasm. We compared nebivolol versus diltiazem in improving coronary vasospasm and quality of life in patients with hypertensive vasospastic angina during a 12-week follow-up. METHODS: Fifty-one hypertensive patients with documented coronary vasospasm were randomly allocated into 3 treatment groups: (1) Nebivolol Group (5mg for 2 weeks/10mg for 10 weeks); (2) Diltiazem Group (90mg for 2 weeks/180mg for 10 weeks); (3) Low-dose Combination Group (2.5mg + 45mg for 2 weeks/5mg + 90mg for 10 weeks). The primary endpoint was to compare the percent changes in coronary vasospasm at 12 weeks from baseline among the 3 groups. The secondary endpoints included changes in quality of life based on the Seattle Angina Questionnaire and changes in blood pressure at 12 weeks from baseline. RESULTS: Significant improvements in coronary vasospasm were found in all groups; however, the improvement in percent changes in coronary artery spasm was greatest in the Diltiazem Group (50.4±8.8% vs. 67.8±12.8% vs. 46.8±12.3%, Nebivolol Group vs. Diltiazem Group p = 0.008; Nebivolol Group vs. Low-dose Combination Group p = 0.999; Diltiazem Group vs. Low-dose Combination Group p = 0.017). The overall Seattle Angina Questionnaire scores were significantly elevated at 12 weeks compared to the baseline in entire study population. There were no significant differences between the three groups in the overall Seattle Angina Questionnaire score changes and blood pressure changes. CONCLUSIONS: Both nebivolol and diltiazem showed significant coronary vasospasm reduction effect, but the effect was greater for diltiazem.


Assuntos
Angina Pectoris/tratamento farmacológico , Vasoespasmo Coronário/tratamento farmacológico , Diltiazem/uso terapêutico , Hipertensão/tratamento farmacológico , Nebivolol/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/complicações , Angina Pectoris/fisiopatologia , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Angiografia Coronária , Vasoespasmo Coronário/etiologia , Vasoespasmo Coronário/fisiopatologia , Citocinas/sangue , Diltiazem/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Nebivolol/administração & dosagem , Óxido Nítrico/metabolismo , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Vasodilatação/efeitos dos fármacos
12.
Front Immunol ; 11: 2014, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849666

RESUMO

To date the pathophysiology of COVID-19 remains unclear: this represents a factor determining the current lack of effective treatments. In this paper, we hypothesized a complex host response to SARS-CoV-2, with the Contact System (CS) playing a pivotal role in innate immune response. CS is linked with different proteolytic defense systems operating in human vasculature: the Kallikrein-Kinin (KKS), the Coagulation/Fibrinolysis and the Renin-Angiotensin (RAS) Systems. We investigated the role of the mediators involved. CS consists of Factor XII (FXII) and plasma prekallikrein (complexed to high-molecular-weight kininogen-HK). Autoactivation of FXII by contact with SARS-CoV-2 could lead to activation of intrinsic coagulation, with fibrin formation (microthrombosis), and fibrinolysis, resulting in increased D-dimer levels. Activation of kallikrein by activated FXII leads to production of bradykinin (BK) from HK. BK binds to B2-receptors, mediating vascular permeability, vasodilation and edema. B1-receptors, binding the metabolite [des-Arg9]-BK (DABK), are up-regulated during infections and mediate lung inflammatory responses. BK could play a relevant role in COVID-19 as already described for other viral models. Angiotensin-Converting-Enzyme (ACE) 2 displays lung protective effects: it inactivates DABK and converts Angiotensin II (Ang II) into Angiotensin-(1-7) and Angiotensin I into Angiotensin-(1-9). SARS-CoV-2 binds to ACE2 for cell entry, downregulating it: an impaired DABK inactivation could lead to an enhanced activity of B1-receptors, and the accumulation of Ang II, through a negative feedback loop, may result in decreased ACE activity, with consequent increase of BK. Therapies targeting the CS, the KKS and action of BK could be effective for the treatment of COVID-19.


Assuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Fibrinólise/imunologia , Sistema Calicreína-Cinina/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Sistema Renina-Angiotensina/imunologia , Bradicinina/metabolismo , Permeabilidade Capilar , Proteína Inibidora do Complemento C1 , Infecções por Coronavirus/virologia , Fator XIIa/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Cininogênio de Alto Peso Molecular/metabolismo , Pandemias , Peptidil Dipeptidase A/metabolismo , Calicreína Plasmática/metabolismo , Pneumonia Viral/virologia , Pré-Calicreína/metabolismo , Receptor B1 da Bradicinina/metabolismo , Receptor B2 da Bradicinina/metabolismo , Vasodilatação
15.
J Vis Exp ; (161)2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32804163

RESUMO

Coronary arterial tone along with the opening or closing of the capillaries largely determine the blood flow to cardiomyocytes at constant perfusion pressure. However, it is difficult to monitor the dynamic changes of the coronary arterioles and the capillaries in the whole heart, primarily due to its motion and non-stop beating. Here we describe a method that enables monitoring of arterial perfusion rate, pressure and the diameter changes of the arterioles and capillaries in mouse right ventricular papillary muscles. The mouse septal artery is cannulated and perfused at a constant flow or pressure with the other dynamically measured. After perfusion with a fluorescently labeled lectin (e.g., Alexa Fluor-488 or -633 labeled Wheat-Germ Agglutinin, WGA), the arterioles and capillaries (and other vessels) in right ventricle papillary muscle and septum could be readily imaged. The vessel-diameter changes could then be measured in the presence or absence of heart contractions. When genetically encoded fluorescent proteins were expressed, specific features could be monitored. For examples, pericytes were visualized in mouse hearts that expressed NG2-DsRed. This method has provided a useful platform to study the physiological functions of capillary pericytes in heart. It is also suitable for studying the effect of reagents on the blood flow in heart by measuring the vascular/capillary diameter and the arterial luminal pressure simultaneously. This preparation, combined with a state-of-the-art optic imaging system, allows one to study the blood flow and its control at cellular and molecular level in the heart under near-physiological conditions.


Assuntos
Arteríolas/diagnóstico por imagem , Capilares/diagnóstico por imagem , Imageamento Tridimensional , Pericitos/fisiologia , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/fisiologia , Capilares/efeitos dos fármacos , Capilares/fisiologia , Cateterismo , Corantes Fluorescentes/metabolismo , Hemodinâmica/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Perfusão , Pericitos/efeitos dos fármacos , Pinacidil/farmacologia , Pressão , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Aglutininas do Germe de Trigo/metabolismo
16.
J Stroke Cerebrovasc Dis ; 29(9): 105011, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807426

RESUMO

The current COVID-19 pandemic has recently brought to attention the myriad of neuro- logic sequelae associated with Coronavirus infection including the predilection for stroke, particularly in young patients. Reversible cerebral vasoconstriction syndrome (RCVS) is a well-described clinical syndrome leading to vasoconstriction in the intracra- nial vessels, and has been associated with convexity subarachnoid hemorrhage and oc- casionally cervical artery dissection. It is usually reported in the context of a trigger such as medications, recreational drugs, or the postpartum state; however, it has not been described in COVID-19 infection. We report a case of both cervical vertebral ar- tery dissection as well as convexity subarachnoid hemorrhage due to RCVS, in a pa- tient with COVID-19 infection and no other triggers.


Assuntos
Betacoronavirus/patogenicidade , Artérias Cerebrais/fisiopatologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Hemorragia Subaracnóidea/complicações , Vasoconstrição , Dissecação da Artéria Vertebral/complicações , Adulto , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/efeitos dos fármacos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Transtornos da Cefaleia Primários/etiologia , Transtornos da Cefaleia Primários/fisiopatologia , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/fisiopatologia , Síndrome , Vasoconstrição/efeitos dos fármacos , Vasodilatação , Dissecação da Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/tratamento farmacológico , Dissecação da Artéria Vertebral/fisiopatologia
17.
Toxicol Lett ; 333: 97-104, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32763312

RESUMO

Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports revealed a significant incidence of toxic events of PPIs including nephritis, osteoporosis, and cardiac damage. Thus, the study was designed to reconcile the deceptive contraindications. The present investigation targeted to reveal the toxic impact of sub-acute and sub-chronic administration of pantoprazole (PPZ) with different concentrations (low dose 4 mg/kg, medium-dose 8 mg/kg and high dose 16 mg/kg once a day) on normal vascular endothelium and renal tissue of rats. Vascular endothelial dysfunction (VED) was estimated by the contractility of an isolated aortic ring, nitrite/nitrate concentration, oxidative stress, and integrity of the endothelium layer. Moreover, the renal abnormalities were further confirmed by an increased level of serum creatinine, blood urea nitrogen (BUN), the incidence of microproteinuria, and structural alteration. Sub-acute administration of PPZ treatment did not produce any toxicological impact on endothelium and renal tissue. Whereas, sub-chronic administration of PPZ treatment causes moderate VED and renal dysfunction in a dose-dependent manner. Sub-chronic treatment of PPZ also influences the mitigation of NO and elevation of oxidative stress. Collecting all the evidence, it concludes that decreased nitric oxide availability and increased levels of oxidative stress may be a possible underlying mechanism of causing VED and renal abnormalities from high-dose PPZ treatment.


Assuntos
Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Rim/efeitos dos fármacos , Pantoprazol/toxicidade , Inibidores da Bomba de Prótons/toxicidade , Administração Oral , Animais , Aorta Torácica/imunologia , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Citocinas/sangue , Relação Dose-Resposta a Droga , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Rim/imunologia , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Nitratos/metabolismo , Nitritos/metabolismo , Ratos , Ratos Wistar , Vasodilatação/efeitos dos fármacos
18.
J Pharmacol Sci ; 144(3): 165-171, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32811745

RESUMO

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) suppresses protein translation. We previously reported eEF2K expression was upregulated in mesenteric arteries (MA) from spontaneously hypertensive rats (SHR). We have recently revealed A484954, an eEF2K inhibitor, acutely suppressed vasopressor agonists-induced increase of blood pressure (BP) in normal Wistar rats. In this study, we examined the acute effects of A484954 on BP in SHR and explored underlying mechanisms. BP was measured by a carotid cannulation method in SHR. Isometric contraction in MA from SHR was measured. Endothelial nitric oxide synthase (eNOS) dimerization was measured by low-temperature sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. A484954 lowered BP in 15-week-old SHR. A484954 induced relaxation in MA from both 4- and 7-9-week-old SHR. In MA from 4-week-old SHR, A484954-induced relaxation was inhibited almost completely by a NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME) and significantly by a ß blocker, propranolol. In MA from 7-9-week-old SHR, on the other hand, A484954-induced relaxation was inhibited partly either by l-NAME, indomethacin, a cyclooxygenase inhibitor, or l-NAME + indomethacin. A484954 promoted the dimerization of eNOS in human endothelial cells. In summary, we have revealed A484954 lowers BP in SHR perhaps through the vasorelaxation via the production of endothelium-derived relaxing factors.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Quinase do Fator 2 de Elongação/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Células Cultivadas , Células Endoteliais/metabolismo , Humanos , Contração Isométrica/efeitos dos fármacos , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Endogâmicos SHR
19.
Metabolism ; 111: 154340, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32791171

RESUMO

BACKGROUND: Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations that give rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction are ill-defined. Increasing evidence suggests that endothelial cells are not a population of uniform cells but are highly heterogeneous and are organized as a communicating multicellular network that controls vascular function. PURPOSE: To investigate the hypothesis that disrupted endothelial heterogeneity and network-level organization contribute to impaired vascular reactivity in obesity. METHODS AND RESULTS: To study obesity-related vascular function without complications associated with diabetes, a state of prediabetic obesity was induced in rats. Small artery diameter recordings confirmed nitric-oxide mediated vasodilator responses were dependent on increases in endothelial calcium levels and were impaired in obese animals. Single-photon imaging revealed a linear relationship between blood vessel relaxation and population-wide calcium responses. Obesity did not alter the slope of this relationship, but impaired calcium responses in the endothelial cell network. The network comprised structural and functional components. The structural architecture, a hexagonal lattice network of connected cells, was unchanged in obesity. The functional network contained sub-populations of clustered specialized agonist-sensing cells from which signals were communicated through the network. In obesity there were fewer but larger clusters of sensory cells and communication path lengths between clusters increased. Communication between neighboring cells was unaltered in obesity. Altered network organization resulted in impaired, population-level calcium signaling and deficient endothelial control of vascular tone. CONCLUSIONS: The distribution of cells in the endothelial network is critical in determining overall vascular response. Altered cell heterogeneity and arrangement in obesity decreases endothelial function and provides a novel framework for understanding compromised endothelial function in cardiovascular disease.


Assuntos
Células Endoteliais/patologia , Endotélio Vascular/patologia , Obesidade/patologia , Estado Pré-Diabético/patologia , Animais , Sinalização do Cálcio/fisiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Masculino , Óxido Nítrico/metabolismo , Obesidade/metabolismo , Estado Pré-Diabético/metabolismo , Ratos , Ratos Wistar , Vasodilatação/fisiologia
20.
J Stroke Cerebrovasc Dis ; 29(9): 104830, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807407

RESUMO

BACKGROUND AND PURPOSE: Nitric oxide (NO) plays a key role in ischemia and shows potential as a biomarker for ischemia. We measured mixed venous nitrite (NO2-) as a proxy for NO, during controlled cerebral ischemia in patients with moyamoya disease (MMD) during direct extracranial/intracranial (EC/IC) bypass surgery with temporary occlusion of the M4 branch of the middle cerebral artery (MCA) to permit anastomosis with the superficial temporal artery (STA). This small, focal ischemic event is not reliably detected using cerebral oximetry, somatosensory evoked potentials (SSEPs) or electroencephalography (EEG). METHODS: We enrolled nine adult MMD patients (n=8 female, n=1 male) undergoing direct EC/IC bypass surgery. Nitrite was measured at least one hour prior to MCA occlusion, and before, during and after anastomosis. Cortical function was monitored using either multi-lead EEG and SSEPs, or frontal EEG activity. RESULTS: Mixed venous NO2- was significantly elevated (p<0.05) within 12 min following arterial occlusion vs. baseline. An M4 branch of the MCA was cross clamped for a median duration of 18 (IQR = 5) minutes during anastomosis. One patient with elevated NO2- showed a transient neurologic deficit that resolved 3 days post-operatively. CONCLUSIONS: Mixed venous NO2- was significantly elevated shortly following cerebral artery occlusion vs. baseline in a majority of the study subjects, suggesting that NO2- is a potential biomarker for ischemia. Since all patients received identical burst suppression anesthesia and vasopressors, the fact that NO2- was not elevated during cross-clamp in all patients supports the conclusion that the NO2- elevation is likely due to ischemia.


Assuntos
Isquemia Encefálica/diagnóstico , Revascularização Cerebral , Artéria Cerebral Média/cirurgia , Doença de Moyamoya/cirurgia , Nitritos/sangue , Artérias Temporais/cirurgia , Oclusão Terapêutica , Adulto , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Revascularização Cerebral/efeitos adversos , Circulação Cerebrovascular , Circulação Colateral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Doença de Moyamoya/sangue , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Valor Preditivo dos Testes , Fatores de Risco , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/fisiopatologia , Oclusão Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Vasodilatação
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