Concurrent exercise training potentiates the effects of angiotensin-converting enzyme inhibitor on regulatory systems of blood pressure control in ovariectomized hypertensive rats.

OBJECTIVE: Enalapril has shown satisfactory potential in controlling increased and sustained blood pressure (BP). However, multiple dysregulated mechanisms that interact with each other and are involved in the pathophysiology of arterial hypertension may not be affected, contributing to the remaining cardiovascular risk. Using an exercise training protocol, we investigated whether adding both approaches to arterial hypertension management could promote higher modulation of regulatory mechanisms of BP in postmenopausal rats. METHODS: Spontaneously hypertensive rats were allocated into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with enalapril maleate (OSE) and trained treated with enalapril maleate (OTE). Both the pharmacological and exercise training protocols lasted for 8 weeks. The BP was directly recorded. Inflammation and oxidative stress were evaluated in the cardiac tissue. RESULTS: Although BP reduction was similar between OSE and OTE, trained group showed lower vasopressor systems outflow after sympathetic ganglion blocking by hexamethonium (mean BP) (OTE: -53.7 ±â€Š9.86 vs. OS: -75.7 ±â€Š19.2 mmHg). Bradycardic and tachycardic response were increased in OTE group (-1.4 ±â€Š0.4 and -2.6 ±â€Š0.4 vs. OS: -0.6 ±â€Š0.3 and -1.3 ±â€Š0.4 bpm/mmHg, respectively), as well as BP variability. In addition, the combination of approaches induced an increase in interleukin 10, antioxidant defense (catalase and glutathione peroxidase) and nitrite levels compared with the OS group. CONCLUSION: Despite similar BP, the inclusion of exercise training in antihypertensive drug treatment exacerbates the positive adaptations induced by enalapril alone on autonomic, inflammatory and oxidative stress profiles, probably affecting end-organ damage and remaining risk.

Parental fructose consumption induces early baroreflex dysfunction in offspring: impact on arterial pressure and on insulin resistance.

Fructose overconsumption is a worldwide trend, and it has been found to cause metabolic disorders in parents and their offspring. Additionally, metabolic syndrome has been closely associated with increased cardiovascular risk. In this study, we hypothesized that the chronic fructose consumption by parents could trigger autonomic dysfunction and cardiometabolic disorders in their offspring. Wistar rats undergo an intake of 10% of fructose in drinking water or regular water for 60 days before mating. Their offspring, control (C) and fructose (F) groups, were evaluated 30 days after weaning. Lower birth weight, increased levels of blood triglycerides and insulin resistance were observed in F compared to C group. The offspring of the fructose parents showed increased mean arterial pressure (C: 104 ± 1 vs. F: 111 ± 2 mmHg) and baroreflex sensitivity impairment, characterized by reduced bradycardic (C: -1.6 ± 0.06 vs. F: -1.3 ± 0.06 bpm/mmHg) and tachycardic responses (C: -4.0 ± 0.1 vs. F: -3.1 ± 0.2 bpm/mmHg). Finally, a higher baroreflex-induced tachycardia was associated with lower insulin tolerance (r = -0.55, P < 0.03) and higher systolic arterial pressure (r = 0.54, P < 0.02). In conclusion, our findings indicate that the excessive consumption of fructose by parents is associated with early autonomic, cardiovascular, and metabolic derangement in the offspring, favoring an increased cardiometabolic risk when they reach adulthood.

Systemic Inflammation and Oxidative Stress in Adults with Bronchiectasis: Association with Clinical and Functional Features.

OBJECTIVES: To compare the inflammatory and oxidative stress (OS) states of adults with bronchiectasis with those of healthy controls and correlate inflammatory and OS levels with lung function and physical capacity. METHODS: This study used a cross-sectional design. Seventy-four adults with bronchiectasis (age: 49±15 years, forced expiratory volume in 1 second [FEV1]: 52.5±25.6%) and 42 healthy controls (age: 44±17 years, FEV1: 95.9±14.0%) performed cardiopulmonary exercise tests and incremental shuttle walking tests. Their physical activity in daily life, inflammatory cytokine, and antioxidant levels in plasma were measured. RESULTS: Compared to that of the controls, the levels of interleukin (IL)-6 (p<0.001), IL-10 (p<0.001), carbonylated proteins (p=0.001), and superoxide anions (p=0.046) were significantly increased in adults with bronchiectasis. Catalase activity was also reduced in this group (p<0.001). The inflammatory markers IL-1ß, IL-6, and tumor necrosis factor-α correlated negatively with aerobic capacity (r=-0.408, r=-0.308, and r=-0.207, respectively). We observed similar correlations with OS markers (thiobarbituric acid and carbonyls; r=-0.290 and r=0.379, respectively), and these markers also significantly correlated with the aerobic capacity. CONCLUSIONS: Adults with bronchiectasis presented an increased systemic inflammatory response that correlated negatively with physical capacity.

The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial.

Background: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 µmol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.

Increased bone resorption by long-term cigarette smoke exposure in animal model.

INTRODUCTION: Clinical and experimental studies have been attesting the deleterious effects of smoking mainly due to the stimulation of osteoclastogenesis and inhibition of osteoblastogenesis. However the physiological mechanisms that can explain these changes are not fully understood. AIMS: To evaluate the trabecular bone resorption effect caused by long-term exposure to cigarette smoke and the action of cytokines and reactive oxygen species involved in this process. METHODS: Sixty young adult C57BL/6 mice were allocated to two groups: control, 30 animals exposed to filtered air for 1, 3 and 6 months; and smoke, 30 animals exposed to cigarette smoke for 1, 3 and 6 months. Femoral and tibial extraction was performed to evaluate the bone mineral matrix, bone cytokines (Receptor activator of nuclear factor-kappa B ligand - RANKL and Osteoprotegerin - OPG) and oxidative stress markers (Thiobarbituric acid reactive substances - Tbars). RESULTS: Exposure to cigarette smoke (CS) generated changes in bone structural parameters in the 6th month of follow-up, demonstrating an evident bone loss; reduction in OPG/RANKL ratio from the 3rd month on and increase in Tbars in the first month, both closely related to the increase in osteoclastogenic activity and bone resorption. CONCLUSION: These findings reinforce the importance of CS-induced oxidative stress in bone compromising the bone cellular activities with a consequent impairment in bone turn over and changes in bone structure.

Systemic inflammation and oxidative stress in adults with bronchiectasis: association with clinical and functional features

OBJECTIVES: To compare the inflammatory and oxidative stress (OS) states of adults with bronchiectasis with those of healthy controls and correlate inflammatory and OS levels with lung function and physical capacity. METHODS: This study used a cross-sectional design. Seventy-four adults with bronchiectasis (age: 49±15 years, forced expiratory volume in 1 second [FEV1]: 52.5±25.6%) and 42 healthy controls (age: 44±17 years, FEV1: 95.9±14.0%) performed cardiopulmonary exercise tests and incremental shuttle walking tests. Their physical activity in daily life, inflammatory cytokine, and antioxidant levels in plasma were measured. RESULTS: Compared to that of the controls, the levels of interleukin (IL)-6 (p<0.001), IL-10 (p<0.001), carbonylated proteins (p=0.001), and superoxide anions (p=0.046) were significantly increased in adults with bronchiectasis. Catalase activity was also reduced in this group (p<0.001). The inflammatory markers IL-1β, IL-6, and tumor necrosis factor-α correlated negatively with aerobic capacity (r=-0.408, r=-0.308, and r=-0.207, respectively). We observed similar correlations with OS markers (thiobarbituric acid and carbonyls; r=-0.290 and r=0.379, respectively), and these markers also significantly correlated with the aerobic capacity. CONCLUSIONS: Adults with bronchiectasis presented an increased systemic inflammatory response that correlated negatively with physical capacity.

Correction: Impact of combined exercise training on the development of cardiometabolic and neuroimmune complications induced by fructose consumption in hypertensive rats.

[This corrects the article DOI: 10.1371/journal.pone.0233785.].

Impact of combined exercise training on the development of cardiometabolic and neuroimmune complications induced by fructose consumption in hypertensive rats.

This study evaluated the impact of combined exercise training on the development of cardiovascular and neuroimmune complications induced by fructose consumption (10% in the drinking water) in hypertensive rats (SHR). After weaning, SHR were divided into 3 groups: SHR (H), SHR+fructose (HF) and SHR+fructose+combined exercise training (treadmill+ladder, 40-60% of maximum capacity) (HFTC). Metabolic, hemodynamic, autonomic, inflammatory and oxidative stress parameters were evaluated in the subgroups (n = 6 group/time) at 7, 15, 30 and 60 days of protocol. Fructose consumption (H vs. HF groups) decreased spontaneous baroreflex sensitivity and total variance of pulse interval at day 7 (7 to 60); increased IL-6 and TNFα in the heart (at day 15, 30 and 60) and NADPH oxidase activity and cardiac lipoperoxidation (LPO) (day 60); increased white adipose tissue weight, reduced insulin sensitivity and increased triglycerides (day 60); induced an additional increase in mean arterial pressure (MAP) (days 30 and 60). Combined exercise training prevented such dysfunctions and sustained increased cardiac IL-10 (day 7) and glutathione redox balance (GSH/GSSG) for the entire protocol. In conclusion, combined exercise training performed simultaneously with exacerbated fructose consumption prevented early cardiovascular autonomic dysfunction, probably trigging positive changes in inflammation and oxidative stress, resulting in a better cardiometabolic profile in rats genetically predisposed to hypertension.

Uma sessão de exercício resistido dinâmico não induz hipotensão pós-exercício em ratas shr / A dynamic resistance exercise session does not induce post-exercise hypotension in female shr rats / Una sesión de ejercicio resistido dinámico no induce hipotensión post-ejercicio en ratas shr hembras

RESUMO Introdução: O exercício resistido dinâmico tem sido recomendado como complemento do aeróbico em indivíduos hipertensos. No entanto, poucos estudos avaliaram os efeitos do exercício resistido nessa população, principalmente em mulheres. Objetivo: Avaliar os efeitos de uma sessão de exercício resistido dinâmico sobre a pressão arterial, a frequência cardíaca e sobre o duplo produto em ratas SHR com hipertensão espontânea. Métodos: Foram utilizadas oito ratas SHR em fase não ovulatória do ciclo estral. Dois dias depois da canulação de artéria carótida, a pressão arterial foi diretamente registrada por 20 minutos no período basal e durante 60 minutos (5 min., 15-30 min., 30-45 min. e 45-60min.) após uma sessão de exercício resistido dinâmico em escada (20%-40% da carga máxima). Resultados: Não foram observadas mudanças na pressão arterial sistólica (basal 191 ± 6,1 vs. recuperação 45-60 min. 191 ± 7,8 mmHg), diastólica (basal 157 ± 2,6 vs. recuperação 45-60 min. 156 ± 3,7 mmHg) e média (basal 174 ± 2,5 vs. recuperação 45-60 min. 173 ± 4,9 mmHg) durante os 60 minutos pós-exercício. No entanto, houve redução da frequência cardíaca (45-60 min. 330 ± 10 vs. 379 ± 15 bpm) e normalização do duplo produto (64390 ± 3529 mmHg.bpm) no período de recuperação com relação ao período basal. Conclusão: Os resultados do presente estudo demonstram que o exercício resistido dinâmico de moderada intensidade induz redução da frequência cardíaca associada à normalização do duplo produto em ratas SHR apesar de não ter sido observada hipotensão pós-exercício. Tais resultados sugerem um bom controle do risco cardiovascular depois uma sessão de exercício resistido dinâmico de moderada intensidade em pacientes hipertensos.

ABSTRACT Introduction: Dynamic resistance exercise has been recommended as an aerobic complement in hypertensive individuals. However, few studies evaluated the effects of resistance exercise in this population, especially in women. Objective: To evaluate the effects of a session of dynamic resistance exercise on blood pressure, heart rate and the double product in SHR female rats with spontaneous hypertension. Methods: We used 8 female SHR rats in the non-ovulatory phases of estrous cycle. Two days after the carotid artery cannulation, blood pressure was recorded for 20 minutes at baseline and for 60 minutes (5 min.; 15-30 min.; 30-45 min. and 45-60min.) after one session of dynamic resistance exercise in a ladder (20-40% of maximum load). Results: There were no changes in systolic blood pressure (baseline: 191±6.1 vs. recovery 45-60min., 191±7.8 mmHg), diastolic (baseline: 157±2.6 vs. recovery 45-60min., 156±3.7 mmHg) and mean blood pressure (baseline: 174±2.5 vs. recovery 45-60min., 173±4.9 mmHg) during the 60 minutes post-exercise. However, there was a reduction in heart rate (45-60min. 330±10 vs. 379±15 bpm) and normalization of the double product (64390±3529 mmHg.bpm) in the recovery period compared to the baseline. Conclusion: The results of the present study demonstrated that moderate-intensity dynamic resistance exercise induces reduced heart rate associated with normalization of the double product in female SHR rats, despite the absence of post-exercise hypotension. These results suggest good control of cardiovascular risk after a dynamic resistance exercise of moderate intensity in hypertensive patients.

RESUMEN Introducción: El ejercicio resistido dinámico ha sido recomendado como complemento del aeróbico en individuos hipertensos. Sin embargo, pocos estudios han evaluado los efectos del ejercicio resistido en esa población, principalmente en mujeres. Objetivo: Evaluar los efectos de una sesión de ejercicio resistido dinámico sobre la presión arterial, la frecuencia cardiaca y sobre el doble producto en ratas SHR hembras con hipertensión espontánea. Métodos: Se utilizaron ocho ratas SHR hembras en fase no ovulatoria del ciclo estral. Dos días después de la canulación de la arteria carótida, la presión arterial fue registrada directamente durante 20 minutos en el período basal y durante 60 minutos (5 min., 15-30 min., 30-45 min. y 45-60 min.) después de una sesión de ejercicio resistido dinámico en escalera (20%-40% de la carga máxima). Resultados: No se observaron cambios en la presión arterial sistólica (basal 191 ± 6,1 vs. recuperación 45-60 min, 191 ± 7,8 mmHg), diastólica (basal 157 ± 2,6 vs. recuperación 45-60 min., 156 ± 3,7 mmHg) y media (basal 174 ±2 ,5 vs. recuperación 45-60 min, 173 ± 4,9 mmHg) durante los 60 minutos posteriores al ejercicio. Sin embargo, hubo reducción de la frecuencia cardiaca (45-60 min. 330 ± 10 vs. 379 ± 15 bpm) y normalización del doble producto (64390 ± 3529 mmHg.bpm) en el período de recuperación con relación al período basal. Conclusión: Los resultados del presente estudio demuestran que el ejercicio resistido dinámico de intensidad moderada induce reducción de la frecuencia cardiaca asociada a la normalización del doble producto en ratas SHR hembras, a pesar de no haber sido observada hipotensión post-ejercicio. Estos resultados indican un buen control del riesgo cardiovascular después de una sesión de ejercicio resistido dinámico de intensidad moderada en pacientes hipertensos.

Autonomic changes in young smokers: acute effects of inspiratory exercise.

PURPOSE: One of the most important consequences of smoking is the development of cardiovascular diseases. However, little is known about the early consequences of smoking and the acute effects of a single inspiratory muscle exercise session (IME). We evaluated the acute effects of an IME on cardiac parameters of young smokers. METHODS: Twelve nonsmokers (C) and fifteen smokers [S; 2.08 (1.0-3.2) pack-years] underwent an acute IME. We evaluated blood pressure (BP) and lactate, and we recorded RR interval for posterior analysis of heart rate variability (HRV), before and after IME. RESULTS: At baseline, systolic BP and HRV parameters in time and frequency domains were changed in S group in comparison with the C. Following IME, S group reduced systolic BP (-8 %), low frequency band (LF) (-21.4 %), LF/high frequency (HF) (-57 %), as well as increased RR variance (+105 %) and HF band. CONCLUSIONS: Our findings indicate that a single session of inspiratory muscle exercise was able to both reduce systolic BP and improve parasympathetic and sympathetic modulations in young smokers. The results of the current study highlight the importance of furthering research on this area to better elucidate the acute and chronic effects of inspiratory muscle training on early cardiovascular and pulmonary changes of cigarette smoking.