ESTRESSE OXIDATIVO, ENVELHECIMENTO RENAL E DOENÇA RENAL CRÔNICA TERMINAL

RESUMO:O mundo está passando por uma transformação demográfica. O número de idosos vem aumentando progressivamente nas últimas décadas, levando a um crescente interesse pelo entendimento do processo de envelhecimento, que é universal, complexo e multifacetado. O estresse oxidativo, uma das teorias biológicas do envelhecimento mais aceita na atualidade, pode estar relacionado à senescência renal. Do ponto de vista do envelhecimento renal, sabe-se que o rim apresenta alterações morfológicas e funcionais com o avançar da idade que podem ser agravadas pela presença de comorbidades. A doença renal crônica terminal vem assumindo grande importância para a saúde pública, visto que a sua incidência e prevalência têm aumentado de forma significativa nas últimas décadas, principalmente na população idosa. Objetiva-se abordar a senescência renal e o desenvolvimento da doença renal crônica terminal e as possíveis relações com a teoria do estresse oxidativo.PALAVRAS-CHAVE: Envelhecimento. Radicais Livres. Estresse Oxidativo. Rim. Doença Renal Terminal. ABSTRACT:The world is undergoing a demographic change. The number of elderly has increased progressively in the last few decades, leading to a growing interest in understanding the aging process, which is universal, complex and multifaceted. Oxidative stress, one of the currently most accepted biological theories of aging, may be related to renal senescence. From the standpoint of renal aging it is known that the kidney presents morphological alterations and, as people grow older, they may become worse due to the presence of comorbidities. End stage renal disease has become increasingly important in public health, since its incidence and prevalence have grown significantly in the last few decades, especially in the elderly population. The intention of this paper is to discuss renal senescence and the development of end stage renal disease, and its possible relations with the theory of oxidative stress. KEYWORDS: Aging. Free Radicals. Oxidative Stress. Kidney. ESR

ACE gene dosage determines additional autonomic dysfunction and increases renal angiotensin II levels in diabetic mice

OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II

Cardiac autonomic dysfunction in chronic stroke women is attenuated after submaximal exercise test, as evaluated by linear and nonlinear analysis

Abstract\ud \ud Background\ud We evaluated cardiac autonomic modulation in women with chronic ischemic stroke (at least 4 years post-stroke) at rest and in response to submaximal exercise test.\ud \ud \ud Methods\ud Fourteen post-stroke women (S group) and 10 healthy women (C group) participated in this study. Autonomic modulation (using linear and nonlinear analysis), blood pressure and metabolic variables at rest were evaluated immediately after the exercise test and during the recovery period (20 min). All participants underwent submaximal exercise test on cycle ergometer with gas analysis.\ud \ud \ud Results\ud At rest, the S group displayed higher lactate concentration, systolic (SBP) and diastolic blood pressure (DBP) values when compared to C group. Furthermore, the S group had lower heart rate variability (HRV) in time domain (SDNN: S = 30 ± 5 vs. 40 ± 8 ms; rMSSD: S = 14 ± 2 vs. C = 34 ± 3 ms), decreased high frequency band of pulse interval (S = 8.4 ± 2 vs. 33.1 ± 9 %) and 2V pattern of symbolic analysis (S = 17.3 ± 1 vs. 30 ± 3 %) (both indicators of cardiac vagal modulation) when compared to C group. Immediately after exercise, S group presented higher values of lactate, SBP, DBP and double product when compared to C group, as well as decreased heart rate recovery (HRR) measured at the first, second and third minutes. At recovery time, all HRV parameters in time and frequency domains improved in the S group; however, HF band remained lower when compared to C group.\ud \ud \ud Conclusions\ud After the exercise test, women with chronic stroke presented reduced heart rate variability, reduced cardiac vagal modulation, as well as reduced HRR, while displayed an improvement of heart rate variability and cardiac vagal modulation when compared to their baseline. These results reinforce the importance of a physically active lifestyle for cardiovascular autonomic disorders observed in chronic stroke women.Conselho National de Pesquisa e Desenvolvimento (CNPq-BPQ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Respiratory muscle strength, functional capacity, autonomic cardiovascular control and endothelial function of patients with chronic renal disease

INTRODUÇÃO: A doença renal crônica (DRC) é uma patologia progressiva e debilitante, que apresenta alta mortalidade devido a causas cardiovasculares. Pacientes com DRC apresentam alterações metabólicas e musculares que estão associadas com diminuição da capacidade funcional e baixa tolerância ao exercício, porém pouco se sabe sobre o acometimento da musculatura respiratória desses pacientes. Dessa forma, os objetivos primários deste estudo foram avaliar a força muscular respiratória (FMR) de pacientes com DRC e verificar a existência de associação da força da musculatura inspiratória com fatores de risco cardiovasculares já descritos na DRC. MÉTODOS: A amostra foi composta por pacientes com DRC (estádios 3 ao 5) (grupo DRC, n = 30) e por indivíduos saudáveis (grupo controle, C. n =11). Posteriormente, para fins de comparação, os pacientes com DRC foram divididos em dois grupos: pacientes com DRC em fase não dialítica (estádios 3 e 4 - grupo DRC-ND, n=12) e pacientes com DRC em hemodiálise (estádio 5 - grupo DRC-D, n = 18). Todos os indivíduos realizaram os seguintes procedimentos: manovacuometria digital para mensuração da pressão inspiratória máxima (PImax) e pressão expiratória máxima (PEmax); registro da pressão arterial (PA) batimento a batimento e do eletrocardiograma para mensuração das variáveis hemodinâmicas; registro da atividade simpática nervosa muscular (ANSM); avaliação da composição corporal por meio de bioimpedância; avaliação da velocidade de onda de pulso (VOP) carotídea-femoral; avaliação da função endotelial; teste ergoespirométrico para mensuração da capacidade funcional cardiorrespiratória. Para os indivíduos do grupo DRC-D as avaliações foram sempre realizadas no segundo dia interdialítico da semana. Posteriormente as curvas de pressão arterial registradas foram utilizadas para mensurar a variabilidade da frequência cardíaca (VFC) e da PA e para determinar o barorreflexo espontâneo. RESULTADOS: Os pacientes com DRC apresentam redução da FMR quando comparados ao grupo controle (PImax: DRC= 82,51 ± 24,39 vs. C= 115,20 ± 18,71 cmH2O; PEmax: DRC= 99,64 ± 19,86 vs. C= 138,90 ± 27,08 cmH2O). Não houve diferença nas pressões respiratórias entre os grupos DRC-D e DRC-ND. Além disso, os pacientes com DRC apresentam diminuição da VFC [SDNN: DRC = 19,03 (10,95 - 44,28) vs. C= 45,25 (28,45 - 76,86)ms], aumento do balanço simpatovagal (DRC= 3,42 ± 1,99 vs. C= 1,54 ±1,01), aumento da variância da PA sistólica [DRC= 48,60 (13,38 -149,00) vs. C= 29,76 (15,83 - 49,54) mmHg2, prejuízo tanto da ativação (DRC= 0,40 ± 0,15 vs. C= 0,72 ± 0,10) quanto da sensibilidade barorreflexa (DRC= 7,98 ± 4,37 vs. C= 20,87 ± 10,68 ms/mmHg), bem como, aumento da ANSM (DRC= 20,44 ± 3,88 vs. C= 17,75 ± 1,46 bursts/min). Para a maioria dos índices de VFC o grupo DRC-D apresentou maior comprometimento do que o grupo DRC-ND. Contudo, o balanço simpatovagal, a variância da PA sistólica, a ANSM e a ativação do barorreflexo não foi diferente entre os grupos DRC-D e DRC-ND. Além disso, os pacientes com DRC apresentaram menor consumo de oxigênio que os indivíduos saudáveis (DRC= 29,1 ± 7,76 vs. C= 38,5 ± 7,9 ml/kg/min), redução da função endotelial (DRC= 4,90 ± 4,62 vs. C =8,70 ± 2,19%) e aumento da VOP (DRC= 8,30 (6,15 - 12,2) vs. C= 6,55 (5,4 - 7,8) m/s) quando comparado ao grupo controle, sendo que não foram observadas diferenças entre os grupos DRC-D e DRC-ND para estas variáveis. Quanto a composição corporal, os indivíduos com DRC apresentaram menor massa corporal celular, menor massa magra, maior massa gorda, menor água intracelular, e maior porcentagem de água extracelular quando comparados ao grupo controle. Não foram observadas diferenças na composição corporal entre o grupo DRC-D e DRC-ND. Houve associação positiva entre a força muscular inspiratória e o consumo máximo de oxigênio, bem como entre a PImax e níveis séricos de albumina nos indivíduos com DRC. CONCLUSÕES: Pacientes com DRC, mesmo em fase não dialítica, apresentam comprometimento da FMR, principalmente da PImax, bem como redução da capacidade funcional cardiorrespiratória, sendo que, existe uma associação entre a PImax e o consumo máximo de oxigênio. Além disso, os pacientes com DRC apresentam prejuízo da VFC e da sensibilidade barorreflexa, aumento do balanço simpatovagal, da ANSM e alterações vasculares, que embora pareçam ser mais evidentes nos doentes renais em fase dialítica, já podem ser observadas também na fase pré-dialítica da DRCINTRODUCTION: Chronic kidney disease (CKD) is a progressive and debilitating condition that presents high mortality due to cardiovascular causes. Patients with CKD have metabolic and muscular changes that are associated with decreased functional capacity and low tolerance to exercise, but little is known about the involvement of the respiratory muscles in these population. Thus, the primary objectives of this study were to evaluate the respiratory muscle strength (RMS) of patients with CKD and to verify the existence of an association of inspiratory muscle strength with cardiovascular risk factors already described in CKD. METHODS: The sample consisted of patients with CKD (stages 3 to 5) (CKD group, n = 30) and healthy individuals (control group, C n = 11). For comparison purposes, patients with CKD were divided into two groups: non-dialytic CKD patients (stages 3 and 4 - CKD-ND group, n = 12) and patients with CKD on hemodialysis (stage 5 - group CKD-D, n = 18). All subjects performed the following procedures: digital manovacuometry to measure maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP); recording of blood pressure (BP) beat-to-beat and electrocardiogram for measurement of hemodynamic variables; register of sympathetic nervous muscle activity (SNMA); assessment of body composition by bioimpedance; assessment of carotid-femoral pulse wave velocity (PWV); evaluation of endothelial function; ergospirometric test for measurement of cardiorespiratory functional capacity. For the subjects in the CKD-D group the evaluations were always performed on the second interdialytic day of the week. Subsequently, the recorded blood pressure curves were used to measure heart rate (HRV) and BP variability and to determine spontaneous baroreflex. RESULTS: Patients with CKD had a reduction in RMS when compared to the control group (MIP: CKD = 82.51 ± 24.39 vs. C = 115.20 ± 18.71 cmH2O; MEP: CKD = 99.64 ± 19, 86 vs. C = 138.90 ± 27.08 cm H2O). There was no difference in respiratory pressures between the CKD-D and the CKD-ND groups. In addition, patients with CKD had a decrease in HRV [SDNN: CKD = 19.03 (10.95 - 44.28) vs. C = 45.25 (28.45 - 76.86) ms], increased sympatovagal balance (CKD = 3.42 ± 1.99 vs. C = 1.54 ± 1.01), increased systolic BP variance [CKD = 48.60 (13.38 -149.00) vs. C = 29.76 (15.83 - 49.54) mmHg2, impairment of both activation (CKD = 0.40 ± 0.15 vs C = 0.72 ± 0.10) and baroreflex sensitivity (CKD = 7.98 ± 4.37 vs. C = 20.87 ± 10.68 ms/mmHg), as well as increased SNMA (CKD = 20.44 ± 3.88 vs. C = 17.75 ± 1.46 bursts/min). For most HRV scores, the CKD-D group presented greater impairment than the CKD-ND group. However, sympathovagal balance, systolic BP variance, SNMA and baroreflex activation were not different between the CKD-D and CKD-ND groups. In addition, patients with CKD had lower oxygen consumption than healthy subjects (CKD = 29.1 ± 7.76 vs. C = 38.5 ± 7.9 ml/kg/min), reduction of endothelial function (CKD = 4.90 ± 4.62 vs. C = 8.70 ± 2.19 %) and increased PWV (CKD = 8.30 (6.15 - 12.2) vs. C = 6.55 (5, 4 - 7.8) m/s) when compared to control group, and no differences were observed between the CKD-D and CKD-ND groups for these variables. Regarding body composition, individuals with CKD had lower cellular body mass, lower lean mass, higher fat mass, lower intracellular water, and higher percentage of extracellular water when compared to control group. No differences were observed in body composition between the CKD-D and CKD-ND groups. There was a positive association between inspiratory muscle strength and maximum oxygen consumption, as well as between MIP and serum albumin levels in individuals with CKD. CONCLUSIONS: Patients with CKD, even in the non-dialytic phase, have FMR impairment, mainly MIP, as well as reduction of cardiorespiratory functional capacity, and there is an association between MIP and maximal oxygen consumption in this population. In addition, patients with CKD have impairment of HRV and baroreflex sensitivity, increased sympatovagal balance, SNMA, and vascular alterations, that although they may appear to be more evident in renal dialysis patients, may also be observed in the predialytic phase of DR

ESTRESSE OXIDATIVO, ENVELHECIMENTO RENAL E DOENÇA RENAL CRÔNICA TERMINAL

RESUMO:O mundo está passando por uma transformação demográfica. O número de idosos vem aumentando progressivamente nas últimas décadas, levando a um crescente interesse pelo entendimento do processo de envelhecimento, que é universal, complexo e multifacetado. O estresse oxidativo, uma das teorias biológicas do envelhecimento mais aceita na atualidade, pode estar relacionado à senescência renal. Do ponto de vista do envelhecimento renal, sabe-se que o rim apresenta alterações morfológicas e funcionais com o avançar da idade que podem ser agravadas pela presença de comorbidades. A doença renal crônica terminal vem assumindo grande importância para a saúde pública, visto que a sua incidência e prevalência têm aumentado de forma significativa nas últimas décadas, principalmente na população idosa. Objetiva-se abordar a senescência renal e o desenvolvimento da doença renal crônica terminal e as possíveis relações com a teoria do estresse oxidativo.PALAVRAS-CHAVE: Envelhecimento. Radicais Livres. Estresse Oxidativo. Rim. Doença Renal Terminal. ABSTRACT:The world is undergoing a demographic change. The number of elderly has increased progressively in the last few decades, leading to a growing interest in understanding the aging process, which is universal, complex and multifaceted. Oxidative stress, one of the currently most accepted biological theories of aging, may be related to renal senescence. From the standpoint of renal aging it is known that the kidney presents morphological alterations and, as people grow older, they may become worse due to the presence of comorbidities. End stage renal disease has become increasingly important in public health, since its incidence and prevalence have grown significantly in the last few decades, especially in the elderly population. The intention of this paper is to discuss renal senescence and the development of end stage renal disease, and its possible relations with the theory of oxidative stress. KEYWORDS: Aging. Free Radicals. Oxidative Stress. Kidney. ESR

ACE gene dosage determines additional autonomic dysfunction and increases renal angiotensin II levels in diabetic mice

OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II

Aerobic exercise attenuates dysautonomia, cardiac diastolic dysfunctions, and hemodynamic overload in female mice with atherosclerosis

Abstract Cardiovascular risk increases during the aging process in women with atherosclerosis and exercise training is a strategy for management of cardiac risks in at-risk populations. Therefore, the aims of this study were to evaluate: (1) the influence of the aging process on cardiac function, hemodynamics, cardiovascular autonomic modulation, and baroreflex sensitivity in females with atherosclerosis at the onset of reproductive senescence; and (2) the impact of exercise training on age-related dysfunctions in this model. Eighteen Apolipoprotein-E knockout female mice were divided equally into young (Y), middle-aged (MA), and trained middle-aged (MAT). Echocardiographic exams were performed to verify cardiac morphology and function. Cannulation for direct recording of blood pressure and heart rate, and analysis of cardiovascular autonomic modulation, baroreflex sensitivity were performed. The MA had lower cardiac diastolic function (E'/A' ratio), and higher aortic thickness, heart rate and mean arterial pressure, lower heart rate variability and baroreflex sensitivity compared with Y. There were no differences between Y and MAT in these parameters. Positive correlation coefficients were found between aortic wall thickness with hemodynamics data. The aging process causes a series of deleterious effects such as hemodynamic overload and dysautonomia in female with atherosclerosis. Exercise training was effective in mitigating aged-related dysfunctions