Nathalia Bernardes

Autonomic modulation of arterial pressure and heart rate variability in hypertensive diabetic rats

OBJECTIVE The aim of the present study was to evaluate the autonomic modulation of the cardiovascular system in streptozotocin (STZ)-induced diabetic spontaneously hypertensive rats (SHR), evaluating baroreflex sensitivity and arterial pressure and heart rate variability. METHODS Male SHR were divided in control (SHR) and diabetic (SHR+DM, 5 days after STZ) groups. Arterial pressure (AP) and baroreflex sensitivity (evaluated by tachycardic and bradycardic responses to changes in AP) were monitored. Autoregressive spectral estimation was performed for systolic AP (SAP) and pulse interval (PI) with oscillatory components quantified as low (LF:0.2-0.6Hz) and high (HF:0.6-3.0Hz) frequency ranges. RESULTS Mean AP and heart rate in SHR+DM (131+/-3 mmHg and 276+/-6 bpm) were lower than in SHR (160+/-7 mmHg and 330+/-8 bpm). Baroreflex bradycardia was lower in SHR+DM as compared to SHR (0.55+/-0.1 vs. 0.97+/-0.1 bpm/mmHg). Overall SAP variability in the time domain (standard deviation of beat-by-beat time series of SAP) was lower in SHR+DM (3.1+/-0.2 mmHg) than in SHR (5.7+/-0.6 mmHg). The standard deviation of the PI was similar between groups. Diabetes reduced the LF of SAP (3.3+/-0.8 vs. 28.7+/-7.6 mmHg2 in SHR), while HF of SAP were unchanged. The power of oscillatory components of PI did not differ between groups. CONCLUSIONS These results show that the association of hypertension and diabetes causes an impairment of the peripheral cardiovascular sympathetic modulation that could be, at least in part, responsible for the reduction in AP levels. Moreover, this study demonstrates that diabetes might actually impair the reduced buffer function of the baroreceptors while reducing blood pressure.

Positive effect of combined exercise training in a model of metabolic syndrome and menopause: autonomic, inflammatory, and oxidative stress evaluations.

It is now well established that after menopause cardiometabolic disorders become more common. Recently, resistance exercise has been recommended as a complement to aerobic (combined training, CT) for the treatment of cardiometabolic diseases. The aim of this study was to evaluate the effects of CT in hypertensive ovariectomized rats undergoing fructose overload in blood pressure variability (BPV), inflammation, and oxidative stress parameters. Female rats were divided into the following groups (n = 8/group): sedentary normotensive Wistar rats (C), and sedentary (FHO) or trained (FHOT) ovariectomized spontaneously hypertensive rats undergoing and fructose overload. CT was performed on a treadmill and ladder adapted to rats in alternate days (8 wk; 40-60% maximal capacity). Arterial pressure (AP) was directly measured. Oxidative stress and inflammation were measured on cardiac and renal tissues. The association of risk factors (hypertension + ovariectomy + fructose) promoted increase in insulin resistance, mean AP (FHO: 174 ± 4 vs. C: 108 ± 1 mmHg), heart rate (FHO: 403 ± 12 vs. C: 352 ± 11 beats/min), BPV, cardiac inflammation (tumor necrosis factor-α-FHO: 65.8 ± 9.9 vs. C: 23.3 ± 4.3 pg/mg protein), and oxidative stress cardiac and renal tissues. However, CT was able to reduce mean AP (FHOT: 158 ± 4 mmHg), heart rate (FHOT: 303 ± 5 beats/min), insulin resistance, and sympathetic modulation. Moreover, the trained rats presented increased nitric oxide bioavailability, reduced tumor necrosis factor-α (FHOT: 33.1 ± 4.9 pg/mg protein), increased IL-10 in cardiac tissue and reduced lipoperoxidation, and increased antioxidant defenses in cardiac and renal tissues. In conclusion, the association of risk factors promoted an additional impairment in metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters and combined exercise training was able to attenuate these dysfunctions.

Cardiovascular autonomic dysfunction and oxidative stress induced by fructose overload in an experimental model of hypertension and menopause

BackgroundMetabolic syndrome is characterized by the association of 3 or more risk factors, including: abdominal obesity associated with an excess of abdominal fat, insulin resistance, type 2 diabetes, dyslipidemia and hypertension. Moreover, the prevalence of hypertension and metabolic dysfunctions sharply increases after the menopause. However, the mechanisms involved in these changes are not well understood. Thus, the aim of this study was to assess the effects of fructose overload on cardiovascular autonomic modulation, inflammation and cardiac oxidative stress in an experimental model of hypertension and menopause.MethodsFemale SHR rats were divided into (n = 8/group): hypertensive (H), hypertensive ovariectomized (HO) and hypertensive ovariectomized undergoing fructose overload (100 g/L in drinking water) (FHO). Arterial pressure (AP) signals were directly recorded. Cardiac autonomic modulation was evaluated by spectral analysis. Oxidative stress was evaluated in cardiac tissue.ResultsAP was higher in the FHO group when compared to the other groups. Fructose overload promoted an increase in body and fat weight, triglyceride concentration and a reduction in insulin sensitivity. IL-10 was reduced in the FHO group when compared to the H group. TNF-α was higher in the FHO when compared to all other groups. Lipoperoxidation was higher and glutathione redox balance was reduced in the FHO group when compared to other groups, an indication of increased oxidative stress. A negative correlation was found between IL-10 and adipose tissue.ConclusionFructose overload promoted an impairment in cardiac autonomic modulation associated with inflammation and oxidative stress in hypertensive rats undergoing ovarian hormone deprivation.

Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats.

OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n = 8), fructose (n = 8), and fructose+simvastatin (n = 8). Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks). Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4±0.32%/min) relative to that in the control group (4.4±0.29%/min). Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4±0.66%/min). The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124±2 mmHg and fructose+simvastatin: 126±3 mmHg vs. controls: 112±2 mmHg). The sympathetic effect was enhanced in the fructose group (73±7 bpm) compared with that in the control (48±7 bpm) and fructose+simvastatin groups (31±8 bpm). The vagal effect was increased in fructose+simvastatin animals (84±7 bpm) compared with that in control (49±9 bpm) and fructose animals (46±5 bpm). CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results support the hypothesis that statins reduce the cardiometabolic risk in females with metabolic syndrome.

Red and Infrared Low-Level Laser Therapy Prior to Injury with or without Administration after Injury Modulate Oxidative Stress during the Muscle Repair Process

Introduction Muscle injury is common among athletes and amateur practitioners of sports. Following an injury, the production of reactive oxygen species (ROS) occurs, which can harm healthy muscle fibers (secondary damage) and delay the repair process. Low-level laser therapy (LLLT) administered prior to or following an injury has demonstrated positive and protective effects on muscle repair, but the combination of both administration times together has not been clarified. Aim To evaluate the effect of LLLT (660 nm and 780 nm, 10 J/cm², 40 mW, 3.2 J) prior to injury with or without the administration after injury on oxidative stress during the muscle repair process. Methods Wistar rats were divided into following groups: control; muscle injury alone; LLLT 660 nm + injury; LLLT 780 nm + injury; LLLT 660 nm before and after injury; and LLLT 780 nm before and after injury. The rats were euthanized on days 1, 3 and 7 following cryoinjury of the tibialis anterior (TA) muscle, which was then removed for analysis. Results Lipid peroxidation decreased in the 660+injury group after one day. Moreover, red and infrared LLLT employed at both administration times induced a decrease in lipid peroxidation after seven days. CAT activity was altered by LLLT in all periods evaluated, with a decrease after one day in the 780+injury+780 group and after seven days in the 780+injury group as well as an increase in the 780+injury and 780+injury+780 groups after three days. Furthermore, increases in GPx and SOD activity were found after seven days in the 780+injury+780 group. Conclusion The administration of red and infrared laser therapy at different times positively modulates the activity of antioxidant enzymes and reduces stress markers during the muscle repair process.

IMPACT OF COMBINED EXERCISE TRAINING ON CARDIOVASCULAR AUTONOMIC CONTROL AND MORTALITY IN DIABETIC OVARIECTOMIZED RATS

The purpose of this study was to compare the effects of aerobic, resistance, or combined exercise training on cardiovascular autonomic control and mortality in diabetic ovariectomized rats. Female Wistar rats were divided into one of five groups: euglycemic sedentary (ES), diabetic ovariectomized sedentary (DOS), diabetic ovariectomized aerobic-trained (DOTA), diabetic ovariectomized resistance-trained (DOTR), or diabetic ovariectomized aerobic+resistance-trained (DOTC). Arterial pressure (AP) was directly recorded and baroreflex sensitivity was evaluated by heart rate responses to AP changes. Cardiovascular autonomic modulation was evaluated by spectral analyses. No differences were observed in body weight and glycemia between diabetic rats. Animals in the DOTC and DOTA groups exhibited an increase in running time, whereas animals in the DOTC and DOTR groups showed greater strength. Trained groups exhibited improvement in total power and the high-frequency band of pulse interval and reduced mortality (vs. DOS). Animals in the DOTC (bradycardic and tachycardic responses) and DOTA (tachycardic responses) groups exhibited attenuation in baroreflex dysfunction that was observed in DOS and DOTR animals, and an improvement in AP variance. In conclusion, all training protocols led to reduced mortality, which may be due to an increase in physical capacity and to cardiovascular and autonomic benefits following training, regardless of any improvement in glycemic control. In this model, the aerobic and combined trainings seem to promote additional cardiovascular autonomic benefits when compared with resistance training alone.

Resistance or aerobic training decreases blood pressure and improves cardiovascular autonomic control and oxidative stress in hypertensive menopausal rats

We investigated whether resistance training (RT) vs. aerobic training (AT) differentially impacts on arterial pressure and related mechanisms in ovariectomized spontaneously hypertensive rats (SHRs). Female SHRs were ovariectomized and assigned to one of the following groups: sedentary, AT, or RT; sham sedentary SHR were used as control group. AT was performed on a treadmill, whereas RT was performed on a vertical ladder. Both exercise protocols were performed for 8 wk, 5 days/wk. Arterial pressure, baroreflex sensitivity, autonomic modulation, and cardiac oxidative stress parameters (lipid peroxidation, protein oxidation, redox balance, NADPH oxidase, and antioxidant enzymes activities) were analyzed. Ovariectomy increased mean arterial pressure (∼9 mmHg), sympathetic modulation (∼40%), and oxidative stress in sedentary rats. Both RT and AT reduced mean arterial pressure (∼20 and ∼8 mmHg, respectively) and improved baroreflex sensitivity compared with sedentary ovariectomized rats. However, RT-induced arterial pressure decrease was significantly less pronounced than AT. Lipid peroxidation and protein oxidation were decreased while antioxidant enzymes were increased in both trained groups vs. sedentaries. The reduced gluthatione was higher after AT vs. other groups, whereas oxidized gluthatione was lower after RT vs. AT. Moreover, sympathetic and parasympathetic modulations were highly correlated with cardiac oxidative stress parameters. In conclusion, both RT and AT can decrease arterial pressure in a model of hypertension and menopause; although, at different magnitudes this decrease was related to attenuated autonomic dysfunction in association with cardiac oxidative stress improvement in both exercise protocols.

Excessive consumption of fructose causes cardiometabolic dysfunctions through oxidative stress and inflammation

A rapid rise in obesity, as well as physical inactivity, in industrialized countries is associated with fructose-consumption-mediated metabolic syndrome having a strong association with cardiovascular disease. Although insulin resistance is thought to be at the core, visceral obesity, hypertension, and hypertriglyceridemia are also considered important components of this metabolic disorder. In addition, various other abnormalities such as inflammation, oxidative stress, and elevated levels of uric acid are also part of this syndrome. Lifestyle changes through improved physical activity, as well as nutrition, are important approaches to minimize metabolic syndrome and its deleterious effects.

Pleiotropic effects of simvastatin in physically trained ovariectomized rats

This study tested the hypothesis that simvastatin treatment can improve cardiovascular and autonomic functions and membrane lipoperoxidation, with an increased effect when applied to physically trained ovariectomized rats. Ovariectomized rats were divided into sedentary, sedentary+simvastatin and trained+simvastatin groups (n = 8 each). Exercise training was performed on a treadmill for 8 weeks and simvastatin (5 mg/kg) was administered in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated based on heart and liver lipoperoxidation using the chemiluminescence method. The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2 mmHg) compared to the sedentary group (122 ± 1 mmHg). Furthermore, the trained group showed lower BP and heart rate compared to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin-treated groups. The vagal effect was increased in the trained+simvastatin group and the sympathetic effect was decreased in the sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (≈21%) and trained+simvastatin groups (≈57%) compared to the sedentary group. Correlation analysis involving all animals demonstrated that cardiac lipoperoxidation was negatively related to the vagal effect (r = -0.7) and positively correlated to the sympathetic effect (r = 0.7). In conclusion, improvement in cardiovascular and autonomic functions associated with a reduction of lipoperoxidation with simvastatin treatment was increased in trained ovariectomized rats.

Hypertension induces additional cardiometabolic impairments and attenuates aerobic exercise training adaptations in fructose-fed ovariectomized rats

We tested whether hypertension favors the development of additional cardiometabolic changes in fructose-fed ovariectomized rats and how it affects aerobic exercise training (ET) effects. All rats received fructose in drinking water (10%) beginning at weaning, were ovariectomized at 10 weeks of age and divided into the normotensive sedentary (NFOS) and trained (NFOT) and hypertensive sedentary (HFOS) and trained (HFOT) groups. ET was performed on a treadmill. Arterial pressure (AP) was directly recorded; heart rate and AP variabilities were analyzed. Lipoperoxidation (LPO) and antioxidant enzyme levels were measured in the left ventricle. In addition to increased AP levels, when compared with the NFOS group, the hypertensive groups had resting tachycardia, a reduction of 29% in the pulse interval variance (VAR-PI), 19% in RMSSD (root mean square of successive differences, a cardiac parasympathetic index) and 53% in the α-index (spontaneous baroreflex), while the systolic AP variance (VAR-SAP) and its low-frequency band (LF-SAP) were sharply increased. ET did not alter AP levels. Even in the presence of hypertension, ET induced resting bradycardia, decreases of 33% in VAR-SAP and 49% in LF-SAP, and an increase of more than 60% in VAR-PI and the α-index. However, some of these parameters were still impaired relative to those of normotensive rats. LPO was reduced and catalase was increased in both trained groups, with no difference between the normotensive and hypertensive groups. Negative correlations were obtained between LPO and RMSSD (r=−0.60, P<0.05) and α-index (r=−0.63, P<0.05). In conclusion, hypertension augmented the dysfunctions in fructose-fed ovariectomized rats and attenuated metabolic aerobic ET benefits. These changes may be related to cardiovascular autonomic and oxidative stress alterations.