In the present study we evaluated the effects of short-term pyridostigmine bromide (0.14 mg/mL) treatment started early after myocardial infarction (MI) on left ventricular (LV) and autonomic functions in rats. Male Wistar rats were divided into control, pyridostigmine, infarcted and infarcted + pyridostigmine-treated groups. Pyridostigmine was administered in the drinking water, starting immediately after MI or sham operation, for 11 days. Left ventricular function was evaluated indirectly by echocardiography and directly by LV catheterization. Cardiovascular autonomic control was evaluated by baroreflex sensitivity (BRS), heart rate variability (HRV) and pharmacological blockade. All evaluations started after 7 days pyridostigmine treatment and were finalized after 11 days treatment. Pyridostigmine prevented the impairment of +dP/dT and reduced the MI area in infarcted + pyridostigmine compared with infarcted rats (7 ± 3% vs 17 ± 4%, respectively). Mean blood pressure was restored in infarcted + pyridostigmine compared with infarcted rats (103 ± 3 vs 94 ± 3 mmHg, respectively). In addition, compared with the infarcted group, pyridostigmine improved BRS, as evaluated by tachycardic (1.6 ± 0.2 vs 2.5 ± 0.2 b.p.m./mmHg, respectively) and bradycardic (-0.42 ± 0.01 vs -1.9 ± 0.1 b.p.m./mmHg) responses, and reduced the low frequency/high frequency ratio of HRV (0.81 ± 0.11 vs 0.24 ± 0.14, respectively). These improvements are probably associated with increased vagal tone and reduced sympathetic tone in infarcted + pyridostigmine compared with infarcted rats. In conclusion, the data suggest that short-term pyridostigmine treatment started early after MI can improve BRS, HRV and parasympathetic and sympathetic tone in experimental rats. These data may have potential clinical implications because autonomic markers have prognostic significance after MI.

1. Impairmant of baroreflex sensitivity (BRS) has been implicated in the reduction of heart rate variability (HRV) and in the increased risk of death after myocardial infarction (MI). In the present study, we investigated whether the additional impairment in BRS induced by sinoaortic baroreceptor denervation (SAD) in MI rats is associated with changes in the low-frequency (LF) component of HRV and increased mortality rate. 2. Rats were randomly divided into four groups: control, MI, denervated (SAD) and SAD + MI rats. Left ventricular (LV) function was evaluated by echocardiography. Autonomic components were assessed by power spectral analysis and BRS. 3. Myocardial infarction (90 days) reduced ejection fraction (by approximately 42%) in both the MI and SAD + MI groups; however, an increase in LV mass and diastolic dysfunction were observed only in the SAD + MI group. Furthermore, BRS, HRV and the LF power of HRV were reduced after MI, with an exacerbated reduction seen in SAD + MI rats. The LF component of blood pressure variability (BPV) was increased in the MI, SAD and SAD + MI groups compared with the control group. Mortality was higher in the MI groups compared with the non-infarcted groups, with an additional increase in mortality in the SAD + MI group compared with the MI group. Correlations were obtained between BRS and the LF component of HRV and between LV mass and the LF component of BPV. 4. Together, the results indicate that the abolishment of BRS induced by SAD in MI rats further reduces the LF band of HRV, resulting in a worse cardiac remodelling and increased mortality in these rats. These data highlight the importance of this mechanism in the prognosis of patients after an ischaemic event.

OBJECTIVE:High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations.METHODS:Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05.RESULTS:Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6±0.2 vs. C: 4.5±0.2 mg/dl/min), hypertension (mean blood pressure, F: 118±3 vs. C: 104±4 mmHg) and obesity (F: 0.31±0.001 vs. C: 0.29±0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function.CONCLUSION:The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.

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.

Moraes-Silva IC, Mostarda C, Moreira ED, Silva KAS, dos Santos F, de Angelis K, Farah VMA V, Irigoyen MC. Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development. J Appl Physiol 114: 786 -791, 2013. First published January 17, 2013 doi:10.1152/japplphysiol.00586.2012.-High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg·dl Ϫ1 ·min Ϫ1 : F: 3.4 Ϯ 0.2; C: 4.7 Ϯ 0.2; CT: 5.0 Ϯ 0.5 FT: 4.6 Ϯ 0.4), mean BP (in mmHG: F: 117 Ϯ 2; C: 100 Ϯ 2; CT: 98 Ϯ 2; FT: 105 Ϯ 2), and Lee index (in g/mm: F ϭ 0.31 Ϯ 0.001; C ϭ 0.29 Ϯ 0.001; CT ϭ 0.27 Ϯ 0.002; FT ϭ 0.28 Ϯ 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an ϳ50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.fructose; exercise training; autonomic nervous system SEVERAL STUDIES HAVE SHOWN that poor eating habits and a large increase in fructose consumption in recent years has contributed to the epidemic of metabolic syndrome (2, 5). These unhealthy habits may result in physiological changes that contribute to a higher morbidity and mortality in humans (14). Among these changes, increase of blood pressure, plasma lipids, obesity, glucose intolerance, insulin resistance, and hyperinsulinemia are the most evident. Additionally, studies have shown an association between these factors as hyperinsulinemia and hypertension, in both humans and animals (10, 21, 36), indicating that once these alterations are present, the higher is the incidence of cardiovascular diseases.Autonomic nervous system dysfunction also accompanies these metabolic disturbances. Our research group has ...