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CONTEXT: Vascular changes can be a risk factor for recurrent and new events of stroke. However, few information is known regarding the variables related to aortic pulse wave morphology in stroke individuals. OBJECTIVE: To analyze aortic pulse wave morphology (arterial stiffness indices, hemodynamics and vascular variables) and to compare the paretic and non-paretic sides in individuals after chronic stroke. DESIGN: In this cross-sectional study stroke individuals had arterial stiffness indices, hemodynamics and vascular variables assessed with brachial artery oscillometry. T-test (CI95%) was used in order to compare the variables between the paretic and non-paretic sides. RESULTS: Twenty individuals were included, 65% men (60.3 SD 16.7 years). The following variables: (mean difference [CI95%]): coefficient of reflection (-2.33 [-4.60 to -0.07]), peak of ejection wave, P1 (5.32 [2.75 to 7.90] and peak of ejection wave, P2 (6.17 [2.55 to 9.78]), central diastolic blood pressure (mean difference [IC95%]): (-3.75 [-6.09 to -1.40]), central systolic blood pressure (-6.17 [-9.74 to -2.59]), mean arterial pressure (-4.46 [-7.08 to -1.84]), peripheral diastolic blood pressure (-3.48 [-5.94 to -1.02]) and peripheral systolic blood pressure (-5.53 [-9.54 to -1.52]) were higher in paretic than non-paretic side. Hemodynamics parameters were similar in both sides. CONCLUSIONS: In this study we demonstrated, for the first time, that many parameters from aortic pulse wave were higher in paretic compared with non-paretic side in individuals after chronic stroke, suggesting that peripheral vascular changes affect heart-vascular coupling in these individuals.
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Background: The changes in endothelial function, arterial stiffness, and heart rate variability (HRV) produced in the first trimester of pregnancy in women who develop gestational hypertension (GH) are still being investigated. Objective: to evaluate the HVR, endothelial function, and arterial stiffness changes during the first trimester of pregnancy and their relationship with the development of GH. Methods: A group of women normotensive during the first trimester (n = 43), who later did (GH; n = 11) or did not (no-GH; n = 32) develop GH in that pregnancy, were enrolled. In the first trimester, endothelial function and arterial stiffness were evaluated through photoplethysmography. HRV, parasympathetic (PNS), and sympathetic (SNS) indexes were measured in a 5-minute continuous electrocardiogram record at rest sitting. The Griess reaction measured urinary nitrite excretion (NOx). Results: Systolic blood pressure (SBP) values were higher in GH (no-GH: 105.8 ± 2.0 vs. GH: 112.7 ± 3.0 mmHg; p < 0.05). Endothelial function was decreased, and arterial stiffness was increased in GH. Only in GH the arterial stiffness was correlated with SBP (Pearson's r: 0.5594; 95%CI: 0.06106-0.8681; p < 0.05). In HRV, GH decreased low-frequency power and the ratio SD2/SD1. The inhibition of PNS was lower in GH. The NOx was reduced in GH (no-GH: 3.4 ± 0.4 vs. GH: 0.3 ± 0.1 µM/L; p < 0.001). NOx was correlated negatively with the SNS index only in GH. Conclusions: Developed GH is preceded early in pregnancy by endothelial dysfunction and increased arterial stiffness. In this context, there are SNS-PNS interrelation modifications with less inhibition of PNS.
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Background: Sirtuin 1 (SIRT1) has been associated with longevity and protection against cardiometabolic diseases, but little is known about how it influences human vascular function. Therefore, this study evaluated the effects of SIRT1 activation by resveratrol and energy restriction on vascular reactivity in adults. Methods: A randomized trial allocated 48 healthy adults (24 women and 24 men), aged 55 to 65 years, to resveratrol supplementation or energy restriction for 30 days. Blood lipids, glucose, insulin, C-reactive protein, noradrenaline, SIRT1 (circulating and gene expression), and flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD) were measured. Results: Both interventions increased circulating SIRT1 (p < 0.001). Pre- and post-tests changes of plasma noradrenaline were significant for both groups (resveratrol: p = 0.037; energy restriction: p = 0.008). Baseline circulating SIRT1 was inversely correlated with noradrenaline (r = -0.508; p < 0.01), and post-treatment circulating SIRT1 was correlated with NMD (r = 0.433; p < 0.01). Circulating SIRT1 was a predictor of FMD in men (p = 0.045), but not in women. SIRT1 was an independent predictor of NMD (p = 0.026) only in the energy restriction group. Conclusions: Energy restriction and resveratrol increased circulating SIRT1 and reduced sympathetic activity similarly in healthy adults. SIRT1 was independently associated with NMD only in the energy restriction group.
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Sirtuína 1 , Estilbenos , Masculino , Adulto , Humanos , Feminino , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Glucose/metabolismo , Lipídeos , Insulina , Estilbenos/farmacologiaRESUMO
The cytokine storm in SARS-CoV-2 infection contributes to the onset of inflammation and target-organ damage. The endothelium is a key player in COVID-19 pathophysiology and it is an important target for cytokines. Considering that cytokines trigger oxidative stress and negatively impact endothelial cell function, we sought to determine whether serum from individuals with severe COVID-19 decreases endothelial cells' main antioxidant defense, i.e., the antioxidant transcriptional factor Nrf2. Human umbilical vein endothelial cells (HUVECs) were incubated with serum from patients with severe COVID-19 at different time points and the effects on redox balance and Nrf2 activity were determined. Serum from individuals with COVID-19 increased oxidant species, as indicated by higher DHE (dihydroethydine) oxidation, increased protein carbonylation, and induced mitochondrial reactive oxygen species (ROS) generation and dysfunction. Serum from patients with COVID-19, but not serum from healthy individuals, induced cell death and diminished nitric oxide (NO) bioavailability. In parallel, Nrf2 nuclear accumulation and the expression of Nrf2-targeted genes were decreased in endothelial cells exposed to serum from individuals with COVID-19. In addition, these cells exhibited higher expression of Bach-1, a negative regulator of Nrf2 that competes for DNA binding. All events were prevented by tocilizumab, an IL-6 receptor blocker, indicating that IL-6 is key to the impairment of endothelial antioxidant defense. In conclusion, endothelial dysfunction related to SARS-CoV-2 infection is linked to decreased endothelial antioxidant defense via IL-6-dependent mechanisms. Pharmacological activation of Nrf2 may decrease endothelial cell damage in individuals with severe COVID-19.NEW & NOTEWORTHY We demonstrate that endothelial cell dysfunction in SARS-CoV-2-infected individuals is linked to decreased activity of the major antioxidant system regulator, the Nrf2 transcription factor. We provide evidence that this phenomenon relies on IL-6, an important cytokine involved in the pathophysiology of COVID-19. Our data support the view that Nrf2 activation is a potential therapeutical strategy to prevent oxidative stress and vascular inflammation in severe cases of COVID-19.
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Antioxidantes , COVID-19 , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Regulação para Baixo , Síndrome da Liberação de Citocina , Interleucina-6/metabolismo , Células Cultivadas , SARS-CoV-2/metabolismo , Estresse Oxidativo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Citocinas/metabolismoRESUMO
Vascular system is a complex network in which different cell types and vascular segments must work in concert to regulate blood flow distribution and arterial blood pressure. Although paracrine/autocrine signaling is involved in the regulation of vasomotor tone, direct intercellular communication via gap junctions plays a central role in the control and coordination of vascular function in the microvascular network. Gap junctions are made up by connexin (Cx) proteins, and among the four Cxs expressed in the cardiovascular system (Cx37, Cx40, Cx43, and Cx45), Cx40 has emerged as a critical signaling pathway in the vessel wall. This Cx is predominantly found in the endothelium, but it is involved in the development of the cardiovascular system and in the coordination of endothelial and smooth muscle cell function along the length of the vessels. In addition, Cx40 participates in the control of vasomotor tone through the transmission of electrical signals from the endothelium to the underlying smooth muscle and in the regulation of arterial blood pressure by renin-angiotensin system in afferent arterioles. In this review, we discuss the participation of Cx40-formed channels in the development of cardiovascular system, control and coordination of vascular function, and regulation of arterial blood pressure.
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Pressão Arterial , Sistema Cardiovascular , Conexinas/metabolismo , Junções Comunicantes/metabolismo , Sistema Cardiovascular/metabolismo , Endotélio Vascular/metabolismo , Proteína alfa-5 de Junções ComunicantesRESUMO
Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe-induced contractions were observed in endothelium-intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP-2) were observed in Sevo, but not in the Iso group. While reduced IL-10 and IL-1ß were observed in Sevo, increases in IL-1ß in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP-2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.
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Anestesia , Anestésicos Inalatórios , Isoflurano , Éteres Metílicos , Ratos , Animais , Isoflurano/toxicidade , Sevoflurano , Metaloproteinase 2 da Matriz , Éteres Metílicos/toxicidade , Anestésicos Inalatórios/toxicidade , Ratos WistarRESUMO
Uncontrolled vasodilation is known to account for hypotension in the advanced stages of sepsis and other systemic inflammatory conditions, but the mechanisms of hypotension in earlier stages of such conditions are not clear. By monitoring hemodynamics with the highest temporal resolution in unanesthetized rats, in combination with ex-vivo assessment of vascular function, we found that early development of hypotension following injection of bacterial lipopolysaccharide is brought about by a fall in vascular resistance when arterioles are still fully responsive to vasoactive agents. This approach further uncovered that the early development of hypotension stabilized blood flow. We thus hypothesized that prioritization of the local mechanisms of blood flow regulation (tissue autoregulation) over the brain-driven mechanisms of pressure regulation (baroreflex) underscored the early development of hypotension in this model. Consistent with this hypothesis, an assessment of squared coherence and partial-directed coherence revealed that, at the onset of hypotension, the flow-pressure relationship was strengthened at frequencies (<0.2â Hz) known to be associated with autoregulation. The autoregulatory escape to phenylephrine-induced vasoconstriction, another proxy of autoregulation, was also strengthened in this phase. The competitive demand that drives prioritization of flow over pressure regulation could be edema-associated hypovolemia, as this became detectable at the onset of hypotension. Accordingly, blood transfusion aimed at preventing hypovolemia brought the autoregulation proxies back to normal and prevented the fall in vascular resistance. This novel hypothesis opens a new avenue of investigation into the mechanisms that can drive hypotension in systemic inflammation.
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BACKGROUND: Subclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality. METHODS: A total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages. RESULTS: Among 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use. CONCLUSION: HDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.
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Piezo1 channel is a sensor for shear-stress in the vasculature. Piezo1 activation induces vasodilation, and its deficiency contributes to vascular disorders, such as hypertension. In this study, we aimed to determine whether Piezo1 channel has a functional role in the dilation of pudendal arteries and corpus cavernosum (CC). For this, male Wistar rats were used, and the relaxation of the pudendal artery and CC was obtained using the Piezo1 activator, Yoda1, in the presence and absence of Dooku (Yoda1 antagonist), GsMTx4 (non-selective mechanosensory channel inhibitor) and L-NAME (nitric oxide synthase inhibitor). In the CC, Yoda1 was also tested in the presence of indomethacin (non-selective COX inhibitor) and tetraethylammonium (TEA, non-selective potassium channel inhibitor). The expression of Piezo1 was confirmed by Western blotting. Our data show that Piezo1 activation leads to the relaxation of the pudendal artery and CC as the chemical activator of Piezo1, Yoda1, relaxed the pudendal artery (47%) and CC (41%). This response was impaired by L-NAME and abolished by Dooku and GsMTx4 in the pudendal artery only. Indomethacin and TEA did not affect the relaxation induced by Yoda1 in the CC. Limited tools to explore this channel prevent further investigation of its underlying mechanisms of action. In conclusion, our data demonstrate that Piezo1 is expressed and induced the relaxation of the pudendal artery and CC. Further studies are necessary to determine its role in penile erection and if erectile dysfunction is associated with Piezo1 deficiency.
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Although dynamic resistance training (DRT) and isometric handgrip training (IHT) may decrease blood pressure (BP) in hypertensives, the effects of these types of training have not been directly compared, and a possible additive effect of combining IHT to DRT (combined resistance training-CRT), has not been investigated. Thus, this study compared the effects of DRT, IHT and CRT on BP, systemic hemodynamics, vascular function, and cardiovascular autonomic modulation. Sixty-two middle-aged men with treated hypertension were randomly allocated among four groups: DRT (8 exercises, 50% of 1RM, 3 sets until moderate fatigue), IHT (30% of MVC, 4 sets of 2 min), CRT (DRT + IHT) and control (CON - stretching). In all groups, the interventions were administered 3 times/week for 10 weeks. Pre- and post-interventions, BP, systemic hemodynamics, vascular function and cardiovascular autonomic modulation were assessed. ANOVAs and ANCOVAs adjusted for pre-intervention values were employed for analysis. Systolic BP decreased similarly with DRT and CRT (125 ± 11 vs. 119 ± 12 and 128 ± 12 vs. 119 ± 12 mmHg, respectively; P < 0.05), while peak blood flow during reactive hyperaemia (a marker of microvascular function) increased similarly in these groups (774 ± 377 vs. 1067 ± 461 and 654 ± 321 vs. 954 ± 464 mL/min, respectively, P < 0.05). DRT and CRT did not change systemic hemodynamics, flow-mediated dilation, and cardiovascular autonomic modulation. In addition, none of the variables were changed by IHT. In conclusion, DRT, but not IHT, improved BP and microvascular function in treated hypertensive men. CRT did not have any additional effect in comparison with DRT alone.
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Hipertensão , Treinamento Resistido , Masculino , Pessoa de Meia-Idade , Humanos , Pressão Sanguínea/fisiologia , Força da Mão/fisiologia , Hipertensão/terapia , Hemodinâmica/fisiologiaRESUMO
Cadmium exposure is related to several cardiovascular diseases, such as hypertension, atherosclerosis and endothelial dysfunction. However, the toxic effect of cadmium can be dependent on the sex when examined sex in experimental models. The aim of this study was to analyze the effects of cadmium exposure on the cardiovascular system of male and female rodents. The experiments were carried out on both-sexes Wistar at 4 months of age, where from 3 months onwards, cadmium (CdCl2 100 mg/l in placed the drinking water for 30 days) or vehicle delivered (distilled water) was ingested. Before and after 30 days of exposure to cadmium, systolic blood pressure was regularly measured. After exposure, blood was collected to measure dosage of cadmium, in male and female, and estrogen in females. Vascular reactivity to phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) was studied at respective isolated aortic segments. After the period to Cd-exposure, systolic blood pressure was increased only in the male rats. Males also had higher levels of plasma cadmium than those of female rats, and exposure to the metal did not affect the amount of estrogen produced in the female rats. Increased myeloperoxidase (MPO) activity was also observed in both the males and females that had been exposed to the metal. Moreover, exposure to the cadmium reduced the ACh relaxation and increased vascular reactivity to Phe, resulting in an imbalance between nitric oxide superoxide anion in the isolated aorta of male rats. In female rats, sub-chronic cadmium exposure did not modify the vascular reactivity to Phe and neither to the ACh. The present study revealed that the Cd exposure for 30 days induced sex-dependent cardiovascular abnormalities.
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Cádmio , Hipertensão , Ratos , Masculino , Feminino , Animais , Cádmio/toxicidade , Endotélio Vascular/fisiologia , Ratos Wistar , Fenilefrina/farmacologia , Óxido Nítrico/farmacologia , Acetilcolina/farmacologia , Estrogênios/farmacologiaRESUMO
Previous studies have investigated the impact of dietary nitrate on vascular function due to the association between dietary nitrate ingestion and improvement in nitric oxide (NO) bioavailability. Considering that NO can present different effects through vascular beds (macro- vs. microvasculature) due to the specific characteristic (function and morphology) that each vessel exhibits, it is crucial to investigate the effect of dietary nitrate ingestion on the macro- and microvascular function to understand the effect of nitrate on vascular function. For this reason, this review aimed to evaluate the impact of dietary nitrate on macro- and microvascular function in humans. A total of 29 studies were included in the systematic review, of which 19 studies evaluated the effect of nitrate supplementation on macrovascular function, eight studies evaluated the effect on microvascular function, and two studies evaluated the impact on both macro- and microvascular function. The literature suggests that dietary nitrate ingestion seems to improve the vascular function in macrovasculature, whereas microvascular function appears to be modest. Future studies investigating the effect of nitrate ingestion on vascular function should focus on measuring macro- and microvascular function whenever possible so that the impact of nitrate-rich foods on vascular segments could be better understood.
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The development of essential hypertension involves several factors. Vascular dysfunction, characterized by endothelial dysfunction, low-grade inflammation and structural remodeling, plays an important role in the initiation and maintenance of essential hypertension. Although the mechanistic pathways by which essential hypertension develops are poorly understood, several pharmacological classes available on the clinical settings improve blood pressure by interfering in the cardiac output and/or vascular function. This review is divided in two major sections. The first section depicts the major molecular pathways as renin angiotensin aldosterone system (RAAS), endothelin, nitric oxide signalling pathway and oxidative stress in the development of vascular dysfunction. The second section describes the role of some pharmacological classes such as i) RAAS inhibitors, ii) dual angiotensin receptor-neprilysin inhibitors, iii) endothelin-1 receptor antagonists, iv) soluble guanylate cyclase modulators, v) phosphodiesterase type 5 inhibitors and vi) sodium-glucose cotransporter 2 inhibitors in the context of hypertension. Some classes are already approved in the treatment of hypertension, but others are not yet approved. However, due to their potential benefits these classes were included.
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Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/farmacologia , Músculo Liso Vascular/metabolismo , Guanilil Ciclase Solúvel/metabolismo , Neprilisina/metabolismo , Óxido Nítrico/metabolismo , Hipertensão Essencial/tratamento farmacológico , Hipertensão Essencial/metabolismo , Inibidores da Fosfodiesterase 5/uso terapêutico , Receptor de Endotelina A/metabolismo , Hipertensão/metabolismo , Sistema Renina-Angiotensina , Endotelinas/metabolismo , Endotelinas/farmacologia , Endotelinas/uso terapêutico , Antagonistas dos Receptores de Endotelina/farmacologia , Receptores de Angiotensina/metabolismo , Receptores de Angiotensina/uso terapêutico , Glucose/metabolismo , Sódio/metabolismo , Sódio/farmacologia , Sódio/uso terapêuticoRESUMO
INTRODUCTION: Combination antiretroviral therapy (cART) substantially extended the life of people living with HIV (PLHIV). However, prolonged HIV infection and cART increase the risk of comorbidities accelerating age-related muscle, bone, and vascular disorders. This cross-sectional study compared muscle mass and strength, bone mineral density (BMD), and vascular function in middle-aged PLHIV treated with cART vs. non-infected age-matched and older controls. METHODS: After careful screening for secondary diseases and medications, body composition, muscular and vascular function were assessed in 12 PLHIV (43.9±8.7 yrs old; HIV-infection for 16.2±8.6 yrs; on cART for 11.6±9.2 yrs), 12 age-matched (CONT, 43.2±8.5 yrs old), and 12 older (OLDER, 74.4±8.3 yrs old) controls through dual x-ray absorptiometry, isokinetic dynamometry, and venous occlusion plethysmography, respectively. RESULTS: PLHIV and CONT showed similar relative muscle mass (65.3±8.0 vs. 66.9±7.3%, respectively; P= 0.88) and strength (160.7±53.9 vs. 152.0±52.9 N.m-1, respectively; P= 0.90), which were greater than OLDER (80.6±18.8 N.m-1; P= 0.001). Total BMD was similar in PLHIV (1.04±0.13 g.cm-2) and OLDER (1.00±0.15 g.cm-2, P= 0.86), and both groups presented lower values than CONT (1.20±0.13 g.cm-2, P< 0.01). No significant difference across groups was detected for macrovascular reactivity (P= 0.32). CONCLUSION: Age-related osteopenia might be accelerated in middle-aged PLHIV on prolonged cART, as their BMD approached values found in older adults. On the other hand, muscle mass, isokinetic strength, and vasodilation capacity were similar in PLHIV and age-matched uninfected controls.
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Densidade Óssea , Infecções por HIV , Absorciometria de Fóton , Adulto , Idoso , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , MúsculosRESUMO
Children with obesity are at higher risk for developing cardiometabolic diseases that once were considered health conditions of adults. Obesity is commonly associated with cardiometabolic risk factors such as dyslipidemia, hyperglycemia, hyperinsulinemia and hypertension that contribute to the development of endothelial dysfunction. Endothelial dysfunction, characterized by reduced nitric oxide (NO) production, precedes vascular abnormalities including atherosclerosis and arterial stiffness. Thus, early detection and treatment of cardiometabolic risk factors are necessary to prevent deleterious vascular consequences of obesity at an early age. Non-pharmacological interventions including L-Citrulline (L-Cit) supplementation and aerobic training stimulate endothelial NO mediated vasodilation, leading to improvements in organ perfusion, blood pressure, arterial stiffness, atherosclerosis and metabolic health (glucose control and lipid profile). Few studies suggest that the combination of L-Cit supplementation and exercise training can be an effective strategy to counteract the adverse effects of obesity on vascular function in older adults. Therefore, this review examined the efficacy of L-Cit supplementation and aerobic training interventions on vascular and metabolic parameters in obese individuals.
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Doenças Cardiovasculares/prevenção & controle , Citrulina/administração & dosagem , Exercício Físico , Longevidade , Doenças Metabólicas/prevenção & controle , Obesidade/terapia , Adolescente , Adulto , Idoso , Arginina/metabolismo , Aterosclerose/prevenção & controle , Pressão Sanguínea/efeitos dos fármacos , Fatores de Risco Cardiometabólico , Criança , Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Obesidade/fisiopatologia , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto JovemRESUMO
The objective of this study was to analyze the acute effects of breaking up prolonged sitting with isometric exercise on the cardiovascular health of sedentary adults. This is a three-condition randomized crossover trial. The sample was comprised of 17 subjects (11 women; 29 ± 10 years old; 25,1 ± 5,1 kg/m2 ). The participants completed, in randomized order, three experimental conditions (control, breaks with isometric leg extension exercise, and breaks with walking), with the order of the conditions determined through simple automatic randomization. All the conditions had in common a sitting period of 3 h. During the conditions with isometric exercise and walking breaks the participants performed breaks with isometric leg extension exercise and with walking every 30 min, while in the control condition they remained seated with no breaks. Before and after this period, vascular function (primary outcome), blood pressure, and cardiac autonomic modulation (secondary outcomes) were measured. Generalized estimated equations were used to analyze the data. The results did not indicate significant interaction effects for vascular function among experimental conditions (p > 0,05 for all). We also did not find significant interaction effects for systolic or diastolic blood pressure among the conditions (p > 0,05 for all). The heart rate variability parameters did not present significant interaction effects among conditions (p > 0,05 for all). In conclusion, breaking up sitting with isometric exercise does not seem to lead to significant effects on the cardiovascular health of sedentary adults.
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Fenômenos Fisiológicos Cardiovasculares , Exercício Físico/fisiologia , Comportamento Sedentário , Caminhada/fisiologia , Adulto , Estudos Cross-Over , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Perivascular adipose tissue (PVAT) dysfunction is associated with vascular damage in cardiometabolic diseases. Although heart failure (HF)-induced endothelial dysfunction is associated with renin-angiotensin system (RAS) activation, no data have correlated this syndrome with PVAT dysfunction. Thus, the aim of the present study was to investigate whether the hyperactivation of the RAS in PVAT participates in the vascular dysfunction observed in rats with HF after myocardial infarction surgery. Wire myograph studies were carried out in thoracic aorta rings in the presence and absence of PVAT. An anticontractile effect of PVAT was observed in the rings of the control rats in the presence (33%) or absence (11%) of endothelium. Moreover, this response was substantially reduced in animals with HF (5%), and acute type 1 angiotensin II receptor (AT1R) and type 2 angiotensin II receptor (AT2R) blockade restored the anticontractile effect of PVAT. In addition, the angiotensin-converting enzyme 1 (ACE1) activity (26%) and angiotensin II levels (51%), as well as the AT1R and AT2R gene expression, were enhanced in the PVAT of rats with HF. Associated with these alterations, HF-induced lower nitric oxide bioavailability, oxidative stress and whitening of the PVAT, which suggests changes in the secretory function of this tissue. The ACE1/angiotensin II/AT1R and AT2R axes are involved in thoracic aorta PVAT dysfunction in rats with HF. These results suggest PVAT as a target in the pathophysiology of vascular dysfunction in HF and provide new perspectives for the treatment of this syndrome.
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Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Sistema Renina-Angiotensina , Angiotensina II/metabolismo , Animais , Aorta Torácica/patologia , Disponibilidade Biológica , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Insuficiência Cardíaca/complicações , Hemodinâmica , Masculino , Modelos Biológicos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/fisiopatologia , Óxido Nítrico/metabolismo , Estresse Oxidativo , Peptidil Dipeptidase A/metabolismo , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , VasoconstriçãoRESUMO
BACKGROUND: Adjuvant chemotherapy with 5-fluorouracil (5-FU) and oxaliplatin increases recurrence-free and overall survival in patients with colon adenocarcinoma. It is known that these drugs have been associated with cardio- and neurotoxicity. We investigated the effects of 5-FU ± oxaliplatin on cardiac function, vascular responses, neurovascular control, and physical capacity in patients with colon cancer. METHODS: Twenty-nine patients with prior colectomy for stage II-III adenocarcinoma and clinical indication for adjuvant chemotherapy were allocated to receive 5-FU (n = 12) or 5-FU + oxaliplatin (n = 17), according to the oncologist's decision. All the analyses were performed just before and after the end of chemotherapy. Cardiac function was assessed by echocardiography and speckle tracking, and cardiac autonomic control was assessed by heart rate variability (HRV). Vascular endothelial function was assessed by flow-mediated dilation (FMD). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique, and muscle blood flow by venous occlusion plethysmography. Physical capacity was evaluated by cardiopulmonary exercise test. RESULTS: Chemotherapy (pooled data) did not significantly change left ventricular ejection fraction (58 ± 1 vs. 55 ± 2%, p = .14), longitudinal strain (-18 ± 1 vs. -18 ± 1%, p = .66), and HRV. Likewise, chemotherapy did not significantly change FMD, muscle blood flow, and MSNA (33 ± 2 vs. 32 ± 1 bursts/min, p = .31). Physical capacity was not significantly changed in both groups. Similar findings were observed when the patients were subdivided in 5-FU and 5-FU + oxaliplatin treatment groups. 5-FU and 5-FU + oxaliplatin did not significantly change cardiac function, HRV, vascular responses, MSNA, and physical capacity. CONCLUSION: This study provides evidence that adjuvant treatment with 5-FU ± oxaliplatin is well tolerated and does not promote changes compatible with long-term cardiotoxicity. IMPLICATIONS FOR PRACTICE: Adjuvant chemotherapy with 5-fluorouracil (5-FU) and oxaliplatin increases recurrence-free and overall survival in patients with colon adenocarcinoma; however, these drugs have been associated with cardio- and neurotoxicity. This study investigated the effects of these drugs on cardiac function, vascular responses, neurovascular control, and physical capacity in patients with colon cancer. It was found that 5-FU and oxaliplatin did not significantly change cardiac function, cardiac autonomic control, vascular endothelial function, muscle sympathetic nerve activity, and physical capacity. This study provides evidence that adjuvant treatment with 5-FU ± oxaliplatin is well tolerated and does not promote changes compatible with long-term cardiotoxicity.
Assuntos
Neoplasias do Colo , Fluoruracila , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Volume Sistólico , Função Ventricular EsquerdaRESUMO
: Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.