Insulin Treatment Does Not Prevent EARLY Autonomic Cardiovascular and Diastolic Dysfunctions in Streptozotocin-Induced Diabetic Rats.

Recent studies have found increased cardiovascular mortality risk in patients with type 1 diabetes when compared to normoglycemic people, even when they were kept under good glycemic control. However, the mechanisms underlying this condition have yet to be fully understood. Using streptozotocin (STZ)-induced diabetic rats, we evaluated the effects of insulin replacement therapy on cardiac, autonomic, inflammatory, and oxidative stress parameters. Daily treatment with insulin administrated subcutaneously in the STZ-diabetic rats showed a reduction in hyperglycemia (>250 mg/dL) to normalized values. The insulin treatment was effective in preventing alterations in cardiac morphometry and systolic function but had no impact on diastolic function. Also, the treatment was not able to prevent the impairment of baroreflex-tachycardic response and systolic arterial pressure variability (SAP-V). A correlation was found between improvement of these autonomic parameters and higher levels of IL-10 and lower levels of oxidized glutathione. Our findings show that insulin treatment was not able to prevent diastolic, baroreflex, and SAP-V dysfunction, suggesting an outstanding cardiovascular risk, even after obtaining a good glycemic control in STZ-induced diabetic rats. This study shed light on a relatively large population of diabetic patients in need of other therapies to be used in combination with insulin treatment and thus more effectively manage cardiovascular risk.

Food readjustment plus exercise training improves cardiovascular autonomic control and baroreflex sensitivity in high-fat diet-fed ovariectomized mice.

Despite consensus on the benefits of food readjustment and/or moderate-intensity continuous exercise in the treatment of cardiometabolic risk factors, there is little evidence of the association between these two cardiovascular risk management strategies after menopause. Thus, the objective of this study was to evaluate the effects of food readjustment and/or exercise training on metabolic, hemodynamic, autonomic, and inflammatory parameters in a model of loss of ovarian function with diet-induced obesity. Forty C57BL/6J ovariectomized mice were divided into the following groups: high-fat diet-fed - 60% lipids throughout the protocol (HF), food readjustment - 60% lipids for 5 weeks, readjusted to 10% for the next 5 weeks (FR), high-fat diet-fed undergoing moderate-intensity exercise training (HFT), and food readjustment associated with moderate-intensity exercise training (FRT). Blood glucose evaluations and oral glucose tolerance tests were performed. Blood pressure was assessed by direct intra-arterial measurement. Baroreflex sensitivity was tested using heart rate phenylephrine and sodium nitroprusside induced blood pressure changes. Cardiovascular autonomic modulation was evaluated in time and frequency domains. Inflammatory profile was evaluated by IL-6, IL-10 cytokines, and TNF-alpha measurements. Only the exercise training associated with food readjustment strategy induced improved functional capacity, body composition, metabolic parameters, inflammatory profile, and resting bradycardia, while positively changing cardiovascular autonomic modulation and increasing baroreflex sensitivity. Our findings demonstrate that the association of these strategies seems to be effective in the management of cardiometabolic risk in a model of loss of ovarian function with diet-induced obesity.

Combined training is the most effective training modality to improve aerobic capacity and blood pressure control in people requiring haemodialysis for end-stage renal disease: systematic review and network meta-analysis.

QUESTIONS: Do aerobic, resistance and combined exercise training improve aerobic capacity, arterial blood pressure and haemodialysis efficiency in people requiring haemodialysis for end-stage renal disease? Is one exercise training modality better than the others for improving these outcomes? DESIGN: Systematic review with network meta-analysis of randomised trials. PARTICIPANTS: Adults requiring haemodialysis for end-stage renal disease. INTERVENTION: Aerobic training, resistance training, combined training and control (no exercise or placebo). OUTCOME MEASURES: Aerobic capacity, arterial blood pressure at rest, and haemodialysis efficiency. RESULTS: Thirty-three trials involving 1254 participants were included. Direct meta-analyses were conducted first. Aerobic capacity improved significantly more with aerobic training (3.35 ml/kg/min, 95% CI 1.79 to 4.91) and combined training (5.00 ml/kg/min, 95% CI 3.50 to 6.50) than with control. Only combined training significantly reduced systolic (-9 mmHg, 95% CI -13 to -4) and diastolic (-5 mmHg, 95% CI -6 to -3) blood pressure compared to control. Only aerobic training was superior to control for haemodialysis efficiency (Kt/V 0.11, 95% CI 0.02 to 0.20). However, when network meta-analysis was conducted, there were some important different findings. Both aerobic training and combined training again elicited greater improvements in aerobic capacity than control. For systolic blood pressure, combined training was superior to control. For diastolic blood pressure, combined training was superior to aerobic training and control. No modality was superior to control for haemodialysis efficiency. Combined training was ranked as the most effective treatment for aerobic capacity and arterial blood pressure. CONCLUSION: Combined training was the most effective modality to increase aerobic capacity and blood pressure control in people who require haemodialysis. This finding helps to fill the gap created by the lack of head-to-head comparisons of different modalities of exercise in people with end-stage renal disease. REGISTRATION: PROSPERO CRD42015020531.

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.

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.

Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction.

OBJECTIVE: The aim of this study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction in ovariectomized rats submitted to myocardial infarction. METHODS: Female Wistar rats were divided into the following ovariectomized groups: sedentary ovariectomized (SO), trained ovariectomized (TO), sedentary ovariectomized infarcted (SOI), and trained ovariectomized infarcted (TOI). Trained groups were submitted to an exercise training protocol on a treadmill (8 wk). Arterial baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes, and cardiopulmonary baroreflex sensitivity was tested by bradycardic and hypotension responses to serotonin injection. Vagal and sympathetic effects were calculated by pharmacological blockade. RESULTS: Arterial pressure was reduced in the TO in comparison with the SO group and increased in the TOI in relation to the SOI group. Exercise training improved the baroreflex sensitivity in both the TO and TOI groups. The TOI group displayed improvement in cardiopulmonary reflex sensitivity compared with the SOI group at the 16 microg/kg serotonin dose. Exercise training enhanced the vagal effect in both the TO (45%) and TOI (46%) animals compared with the SO and SOI animals and reduced the sympathetic effect in the TOI (38%) in comparison with the SOI animals. Significant correlations were obtained between bradycardic baroreflex responses and vagal (r = -0.7, P < 0.005) and sympathetic (r = 0.7, P < 0.001) effects. CONCLUSIONS: These results indicate that exercise training in ovariectomized rats submitted to myocardial infarction improves resting hemodynamic status and reflex control of the circulation, which may be due to an increase in the vagal component. This suggests a homeostatic role for exercise training in reducing the autonomic impairment of myocardial infarction in postmenopausal women.

Impairment on cardiac output and blood flow adjustments to exercise in L-NAME-induced hypertensive rats.

The objective of the present study was to investigate cardiovascular adjustments at rest, during exercise, and 1 hour after exercise among nitric oxide (NO) blockade-induced hypertensive rats. Male Wistar rats (308 +/- 9 g) assigned as normotensive (n = 9) and hypertensive (N(omega)-nitro-L-arginine methyl ester, n = 11) underwent a bout of exercise. Arterial pressure (AP) and blood oxygen saturation were measured. Colored microspheres were used to evaluate blood flow and cardiac output (CO). Hypertensive rats (143 +/- 5 vs. 102 +/- 4 mmHg in normotensive rats), who presented reduced CO (57 +/- 6 vs. 102 +/- 7 mL/min in normotensive), also presented diminished blood flow in kidney, lung, and muscles at rest in comparison with normotensive rats. Exercise increased AP (20%), heart rate (40%), and CO (32%) among the normotensive rats, whereas the hypertensive rats presented an increased heart rate (40%) accompanied by a reduced venous oxygen saturation (45.5 +/- 2.1% vs. 75 +/- 0.7% in normotensive rats). Muscle vasodilatation, which was observed among the normotensive rats and is considered a hallmark adjustment to exercise, was not observed among the hypertensive rats. After a 1-hour interval from exercise most of the evaluated parameters returned to basal values. In conclusion, exercise did not cause an increase in CO, AP, or blood flow to skeletal muscle in hypertensive rats. However, it was associated with a significant increase in the arterio-venous oxygen content difference in NO-blocked rats, thus suggesting that hypertension associated with impairment in NO release induced different cardiovascular adjustments to exercise.