Maria A. Delbin

Exercise training reduces pulmonary ischaemia–reperfusion-induced inflammatory responses

Physical exercise reduces the deleterious effects of cardiovascular and inflammatory disorders. The purpose of the present study was to evaluate the beneficial effects of physical training on the inflammatory responses following lung ischaemia–reperfusion (IR) in rats. Male Wistar rats were divided into sham-operated animals and sedentary and trained animals submitted to lung IR. The run training programme consisted of 5u2005sessions·week−1, each lasting 60u2005min·day−1, at 66% of maximal oxygen consumption for 8u2005weeks. The left pulmonary artery, bronchus and pulmonary vein were occluded for 90u2005min and reperfused for 2u2005h. Lung protein extravasation was measured as 125I-human albumin accumulation, whereas lung neutrophil infiltration was measured as myeloperoxidase activity. Lung IR in sedentary rats resulted in marked increases in protein extravasation and neutrophil influx, and in significant elevations of serum tumour necrosis factor (TNF)-α and interleukin (IL)-1β levels. Physical preconditioning attenuated the increased IR-induced protein leakage without affecting neutrophil influx. It also reduced serum TNF-α (and IL-1β) levels, but had no effect on IL-10 levels. Plasma superoxide dismutase activity was significantly increased in trained IR rats. The present data show that physical preconditioning protects the rat lung from ischaemia–reperfusion injury by attenuating the pulmonary vascular permeability that may be a consequence of reduced levels of tumour necrosis factor-α and interleukin-1β and elevated superoxide dismutase activity.

Taurine Supplementation Reduces Blood Pressure and Prevents Endothelial Dysfunction and Oxidative Stress in Post-Weaning Protein-Restricted Rats

Introduction Taurine is a sulfur-containing amino acid that exerts protective effects on vascular function and structure in several models of cardiovascular diseases through its antioxidant and anti-inflammatory properties. Early protein malnutrition reprograms the cardiovascular system and is linked to hypertension in adulthood. This study assessed the effects of taurine supplementation in vascular alterations induced by protein restriction in post-weaning rats. Methods and Results Weaned male Wistar rats were fed normal- (12%, NP) or low-protein (6%, LP) diets for 90 days. Half of the NP and LP rats concomitantly received 2.5% taurine supplementation in the drinking water (NPT and LPT, respectively). LP rats showed elevated systolic, diastolic and mean arterial blood pressure versus NP rats; taurine supplementation partially prevented this increase. There was a reduced relaxation response to acetylcholine in isolated thoracic aortic rings from the LP group that was reversed by superoxide dismutase (SOD) or apocynin incubation. Protein expression of p47phox NADPH oxidase subunit was enhanced, whereas extracellular (EC)-SOD and endothelial nitric oxide synthase phosphorylation at Ser 1177 (p-eNOS) were reduced in aortas from LP rats. Furthermore, ROS production was enhanced while acetylcholine-induced NO release was reduced in aortas from the LP group. Taurine supplementation improved the relaxation response to acetylcholine and eNOS-derived NO production, increased EC-SOD and p-eNOS protein expression, as well as reduced ROS generation and p47phox expression in the aortas from LPT rats. LP rats showed an increased aortic wall/lumen ratio and taurine prevented this remodeling through a reduction in wall media thickness. Conclusion Our data indicate a protective role of taurine supplementation on the high blood pressure, endothelial dysfunction and vascular remodeling induced by post-weaning protein restriction. The beneficial vascular effect of taurine was associated with restoration of vascular redox homeostasis and improvement of NO bioavailability.

Differential coronary resistance microvessel remodeling between type 1 and type 2 diabetic mice: Impact of exercise training

The goals of the present study were to compare coronary resistance microvessel (CRM) remodeling between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) mice, and to determine the impact of aerobic exercise training on CRM remodeling in diabetes. Eight week old male mice were divided into T1DM: control sedentary (Control-SD), T1DM sedentary (T1DM-SD) induced by streptozotocin, and T1DM exercise trained (T1DM-TR); T2DM: control sedentary (Db/db-SD), T2DM sedentary (db/db-SD), and T2DM trained (db/db-TR). Aerobic exercise training (TR) was performed on a mouse treadmill for 8weeks. CRMs were isolated and mounted on a pressure myograph to measure and record vascular remodeling and mechanics. CRM diameters, wall thickness, stress-strain, incremental modulus remained unchanged in T1DM-SD mice compared to control, and exercise training showed no effect. In contrast, CRMs isolated from db/db-SD mice exhibited decreased luminal diameter with thicker microvascular walls, which significantly increased the wall:lumen ratio (Db/db-SD: 5.8±0.3 vs. db/db-SD: 8.9±0.7, p<0.001). Compared to db/db-SD mice, coronary arterioles isolated from db/db-TR mice had similar internal diameter and wall thickness, while wall:lumen ratio (6.8±0.2, p<0.05) and growth index (db/db-SD: 16.2 vs. db/db-TR: 4.3, % over Db/db) were reduced. These data show that CRMs undergo adverse inward hypertrophic remodeling only in T2DM, but not T1DM, and that aerobic exercise training can partially mitigate this process.

The diabetic vasculature: physiological mechanisms of dysfunction and influence of aerobic exercise training in animal models.

Diabetes mellitus (DM) is associated with a number of complications of which chronic vascular complications are undoubtedly the most complex and significant consequence. With a significant impact on health care, 50-80% of people with diabetes die of cardiovascular disease (including coronary artery disease, stroke, peripheral vascular disease and other vascular disease), making it the major cause of morbidity and mortality in diabetic patients. A healthy lifestyle is essential in the management of DM, especially the inclusion of aerobic exercise, which has been shown effective in reducing the deleterious effects in vasculature. Interest in exercise studies has increased significantly with promising results that demonstrate a future for investigation. Considering the importance of this emerging field, the aim of this mini-review is to summarize and integrate animal studies investigating physiological mechanisms of vascular dysfunction and remodeling in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and how these are influenced by chronic aerobic exercise training.

Resistance training prevents the cardiovascular changes caused by high-fat diet

AIMSnAerobic exercise is indicated for prevention and treatment of obesity-induced cardiovascular disorders. Although the resistance training (RT) may also produce effects similar to aerobic exercise, this is not completely clear yet. In the present study, we tested if RT in moderate intensity might prevent alterations in blood pressure (BP), sympathetic modulation of systolic blood pressure (SBP), baroreflex function and the changes in renin-angiotensin system (RAS) and cytokines mRNA expression within the nucleus of the tract solitary (NTS) in rats fed with high-fat diet (HFD).nnnMAIN METHODSnMale Holtzman rats (300-320 g) were divided into 4 groups: sedentary with standard chow diet (SED-SD); sedentary with high-fat diet (SED-HFD); RT with standard chow diet (RT-SD); and RT with high-fat diet (RT-HFD). The trained groups performed a total of 10 weeks of moderate intensity RT in a vertical ladder. In the first 3 weeks all experimental groups were fed with SD. In the next 7 weeks, the SED-HFD and RT-HFD groups were fed with HFD.nnnKEY FINDINGSnIn SED-HFD, BP and sympathetic modulation of SBP increased, whereas baroreflex bradycardic responses were attenuated. RT prevented the cardiovascular and inflammatory responses (increases in tumoral necrosis factor-α and interleukin-1β) produced by HFD in SED rats. The anti-inflammatory interleukin-10, angiotensin type 2 receptor, Mas receptor and angiotensin converting enzyme 2 mRNA expressions in the NTS increased in the RT-HFD compared to SED-HFD.nnnSIGNIFICANCEnThe data demonstrated that moderate intensity RT prevented obesity-induced cardiovascular disorders simultaneously with reduced inflammatory responses and modifications of RAS in the NTS.

Aerobic exercise training protects against endothelial dysfunction by increasing nitric oxide and hydrogen peroxide production in LDL receptor-deficient mice

BackgroundEndothelial dysfunction associated with hypercholesterolemia is an early event in atherosclerosis characterized by redox imbalance associated with high superoxide production and reduced nitric oxide (NO) and hydrogen peroxide (H2O2) production. Aerobic exercise training (AET) has been demonstrated to ameliorate atherosclerotic lesions and oxidative stress in advanced atherosclerosis. However, whether AET protects against the early mechanisms of endothelial dysfunction in familial hypercholesterolemia remains unclear. This study investigated the effects of AET on endothelial dysfunction and vascular redox status in the aortas of LDL receptor knockout mice (LDLr−/−), a genetic model of familial hypercholesterolemia.MethodsTwelve-week-old C57BL/6J (WT) and LDLr−/− mice were divided into sedentary and exercised (AET on a treadmill 1xa0h/5xa0×xa0per week) groups for 4xa0weeks. Changes in lipid profiles, endothelial function, and aortic NO, H2O2 and superoxide production were examined.ResultsTotal cholesterol and triglycerides were increased in sedentary and exercised LDLr−/− mice. Endothelium-dependent relaxation induced by acetylcholine was impaired in aortas of sedentary LDLr−/− mice but not in the exercised group. Inhibition of NO synthase (NOS) activity or H2O2 decomposition by catalase abolished the differences in the acetylcholine response between the animals. No changes were noted in the relaxation response induced by NO donor sodium nitroprusside or H2O2. Neuronal NOS expression and endothelial NOS phosphorylation (Ser1177), as well as NO and H2O2 production, were reduced in aortas of sedentary LDLr−/− mice and restored by AET. Incubation with apocynin increased acetylcholine-induced relaxation in sedentary, but not exercised LDLr−/− mice, suggesting a minor participation of NADPH oxidase in the endothelium-dependent relaxation after AET. Consistent with these findings, Nox2 expression and superoxide production were reduced in the aortas of exercised compared to sedentary LDLr−/− mice. Furthermore, the aortas of sedentary LDLr−/− mice showed reduced expression of superoxide dismutase (SOD) isoforms and minor participation of Cu/Zn-dependent SODs in acetylcholine-induced, endothelium-dependent relaxation, abnormalities that were partially attenuated in exercised LDLr−/− mice.ConclusionThe data gathered by this study suggest AET as a potential non-pharmacological therapy in the prevention of very early endothelial dysfunction and redox imbalance in familial hypercholesterolemia via increases in NO bioavailability and H2O2 production.

Heart rate variability and plasma biomarkers in patients with type 1 diabetes mellitus: Effect of a bout of aerobic exercise.

OBJECTIVEnThe aim of this study was to evaluate: (1) the cardiovascular parameters and plasma biomarkers in people with type 1 diabetes mellitus (T1DM) at baseline; and (2) the heart rate variability (HRV) and blood glucose in response to a session of aerobic exercise (AE) and during recovery period.nnnRESEARCH DESIGN AND METHODSnAdults (18-35 years) were divided into two groups: control (CT, n=10) and T1DM (n=9). Anthropometric, cardiovascular, and biochemical parameters, and aerobic capacity (indirect peak oxygen uptake, VO2peak) were evaluated at baseline. Thirty minutes of AE (40-60% intensity) was performed on a treadmill. Blood glucose and HRV were determined at rest, during AE, and during the recovery period.nnnRESULTSnAnthropometric measurements, cardiovascular parameters, aerobic capacity, and biochemical parameters were similar between the groups at baseline. In the T1DM group, blood glucose, glycated hemoglobin, and thiobarbituric acid reactive substances concentrations were increased while nitrite/nitrate (NOx(-)) levels were reduced. During AE, the magnitude of the reduction of blood glucose was greater than that during the recovery period in the T1DM group. The RR intervals and SDNN were reduced at rest as well as in the recovery period in T1DM subjects, whereas the RMSSD and pNN50 were only reduced during the recovery period. No changes were observed in low frequency (LF), high frequency (HF), and LF/HF ratio.nnnCONCLUSIONnOur study shows that T1DM patients on insulin therapy have poor blood glucose control with greater lipid peroxidation and lower NOx(-) levels, accompanied by an imbalance in autonomic function detected by the challenge of AE.

Chronic treatment with resveratrol improves overactive bladder in obese mice via antioxidant activity

The objective of the present work was to evaluate whether oral intake with resveratrol ameliorates overactive bladder in high-fat fed mice. Male C57BL6 mice fed with standard chow or high-fat diet to induce obesity received a two-week therapy with resveratrol (100mg/kg, given as a daily gavage). Weight and metabolic profile, together with cystometry and in vitro bladder contractions were evaluated. Measurements of gp91phox and SOD1 mRNA expressions and reactive-oxygen species (ROS) in bladder tissues, and serum TBARS were performed. Obese mice exhibited increases in body weight and epididymal fat mass, which were significantly reduced by oral treatment with resveratrol. Cystometric study in obese mice showed increases in non-voiding contractions, post-voiding pressure and voiding frequency that were reversed by resveratrol treatment. Likewise, the in vitro bladder overactivity in response to electrical-field stimulation (80V, 1-32Hz) or carbachol (1nM to 10mM) were normalized by resveratrol. The gp91phox and SOD1 mRNA expressions in bladder tissues were markedly higher in obese mice compared with lean group. In addition, ROS levels in bladder tissues and serum lipid peroxidation (TBARS assay) were markedly higher in obese compared with lean mice, all of which were reduced by resveratrol treatment. In lean group, resveratrol had no effect in any parameter evaluated. Our results show that two-week therapy of obese mice with resveratrol reduces the systemic and bladder oxidative stress, and greatly ameliorated the cystometry alterations and in vitro bladder overactivity. Resveratrol treatment could be an option to prevent obesity-associated overactive bladder.

Influence of aerobic exercise training on cardiovascular and endocrine-inflammatory biomarkers in hypertensive postmenopausal women☆

Given that few studies have examined the interaction between endocrine-inflammatory mediators and aerobic exercise training in hypertensive postmenopausal women, the aim of this study was to investigate whether aerobic exercise training (AET) for twenty-four sessions would alter cortisol, leptin and interleukin-1β (IL-1β) levels. To further analyze endothelium function in response to AET, we also examined redox state as well as NO/cGMP pathway in this population. Eighteen hypertensive postmenopausal women finished this study. AET program consisted of 24 sessions in treadmill, 3 times per week, duration of 30 up to 40 min for each session, for 8 weeks at intensity of 100% of the MLSS according to previous incremental test. Heart rate was monitored in all studied time (resting and during exercise sessions). After 48 h of the last exercise session, blood samples were collected for biochemical analyses (levels of cortisol, leptin, IL-1β, nitrite/nitrate (NOx−), cGMP, malondialdehyde (MDA) and asymmetric dimethylarginine (ADMA); superoxide and catalase activity). We also measured systolic and diastolic blood pressure. A significant reduction in body mass was observed. As expected, systolic and diastolic blood pressure values were significantly reduced after AET in hypertensive women. We also found a marked increase in NOx− levels as well as cGMP concentration in trained women, approximately 37.7 and 30.8%, respectively. No changes in cortisol, leptin, ADMA and IL-1β levels were observed after AET. Similarly, MDA levels and catalase activity were not affected by AET. In contrast, a marked increase in SOD activity was found (86.6%). In conclusion, our findings show that aerobic exercise training for twenty-four sessions promoted a significant reduction in blood pressure by activating NO/cGMP pathway as well as by promoting an up-regulation of SOD activity without changing in cortisol/leptin levels in postmenopausal hypertensive women.

Perivascular adipose tissue and vascular responses in healthy trained rats

Abstract Aims The importance of perivascular adipose tissue (PVAT) in vascular function has recently been recognized. The aim of the study was to investigate the effects of exercise training on anticontractile responses of periaortic adipose tissue. Main methods Male Wistar rats were divided into sedentary (SD) and trained (TR). Running training was performed for 60xa0min/day, 5xa0days/week, for 8xa0weeks. Concentration–response curves to acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (PHE) and serotonin (5-HT) were obtained in aortic rings without (PVAT–) or with (PVAT+) PVAT. The protein expressions of eNOS, AMPKα, pAMPKThr172 and mtTFA were determined in PVAT. The contents of adiponectin, leptin and TNF-α were evaluated systemically and locally. Key findings The PVAT+ rings did not modify the relaxing responses to ACh and SNP whereas it showed anticontractile effects for both PHE and 5-HT agents in the SD and TR groups. The amount of PVAT was markedly reduced in TR (3.6xa0±xa00.3xa0mg/mm) compared with SD (6.8xa0±xa00.6xa0mg/mm). Increased protein expressions of eNOS, pAMPKThr172 and mtTFA were observed in PVAT from TR animals, without modifications in PVAT-derived adiponectin, leptin and TNF-α. Circulatory leptin levels were reduced in TR without changes in adiponectin. Significance Our findings show that exercise training for 8xa0weeks did not alter the anticontractile effects induced by PVAT in rat-isolated aorta. Moreover, PVAT-derived adipokine, adiponectin and leptin levels were not different in trained healthy animals despite a significant metabolic adaptation and reduction in periaortic adipose tissue amount.