Involvement of L-type calcium channel and SERCA2a in myocardial dysfunction induced by obesity

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca(2+)) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca(2+) channels and sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca(2+) channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca(2+) channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca(2+) was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca(2+) channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca(2+) channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca(2+) protein levels. J. Cell. Physiol. 226: 2934-2942, 2011. (C) 2011 Wiley-Liss, Inc.

Exercise intensity optimization for men with high cardiorespiratory fitness

Exercise intensity is a key parameter for exercise prescription but the optimal range for individuals with high cardiorespiratory fitness is unknown. The aims of this study were (1) to determine optimal heart rate ranges for men with high cardiorespiratory fitness based on percentages of maximal oxygen consumption (%VO(2max)) and reserve oxygen consumption (%VO(2reserve)) corresponding to the ventilatory threshold and respiratory compensation point, and ( 2) to verify the effect of advancing age on the exercise intensities. Maximal cardiorespiratory testing was performed on 210 trained men. Linear regression equations were calculated using paired data points between percentage of maximal heart rate (%HR(max)) and %VO(2max) and between percentage of heart rate reserve (%HRR) and %VO(2reserve) attained at each minute during the test. Values of %VO(2max) and %VO(2reserve) at the ventilatory threshold and respiratory compensation point were used to calculate the corresponding values of %HRmax and %HRR, respectively. The ranges of exercise intensity in relation to the ventilatory threshold and respiratory compensation point were achieved at 78-93% of HR(max) and 70-93% of HRR, respectively. Although absolute heart rate decreased with advancing age, there were no age-related differences in %HR(max) and %HRR at the ventilatory thresholds. Thus, in men with high cardiorespiratory fitness, the ranges of exercise intensity based on %HR(max) and %HRR regarding ventilatory threshold were 78-93% and 70-93% respectively, and were not influenced by advancing age.

Exercise training associated with diet improves heart rate recovery and cardiac autonomic nervous system activity in obese children

The purpose of this study was to test the hypotheses that in obese children: 1) hypocaloric diet (D) improves both heart rate recovery at 1 min (Delta HRR1) cfter an exercise test, and cardiac autonomic nervous system activity (CANSA) in obese children; 2) Diet and exercise training (DET) combined leads to greater improvement in both Delta HRR1 after an exercise test and in CANSA, than D alone. Moreover, we examined the relationships among Delta HRR1, CANSA, cardiorespiratory fitness and anthropometric variables (AV) in obese children submitted to D and to DET. 33 obese children (10 +/- 0.2 years; body mass index (BMI) >95(th) percentile) were divided into 2 groups: D (n = 15; BMI = 31 +/- 1 kg/m(2)) and DET (n = 18; 29 +/- 1 kg/m(2)). All children performed a maximal cardiopulmonary exercise test on a treadmill. The Delta HRR1 was defined as the difference between heart rate at peak and at 1-min post-exercise. CANSA was assessed using power spectral analysis of heart rate variability at rest. The sympathovagal balance (low frequency and high frequency ratio, LF/HF) was measured. After interventions, all obese children showed reduced body weight (P < 0.05). The D group did not improve in terms of peak VO(2), Delta HRR1 or LF/HF ratio (P > 0.05). In contrast, the DET group showed increased peak VO(2) (P = 0.01) and improved Delta HRR1 (Delta HRR1 = 37.3 +/- 2.6; P = 0.01) and LF/HF ratio (P = 0.001). The DET group demonstrated significant relationships among Delta HRR1, peak VO(2) and CANSA (P < 0.05). In conclusion, DET, in contrast to D, promoted improved Delta HRR1 and CANSA in obese children, suggesting a positive influence of increased levels of cardiorespiratory fitness by exercise training on cardiac autonomic activity.

Atenolol blunts blood pressure increase during dynamic resistance exercise in hypertensives

center dot Dynamic resistance exercise promotes a sizeable increase in blood pressure during its execution in non medicated hypertensives. WHAT THIS STUDY ADDS center dot Atenolol not only decreases blood pressure level but also mitigates the increase of blood pressure during dynamic resistance exercise in hypertensive patients. An increase in blood pressure during resistance exercise might be at least in part attributed to an increase in cardiac output. AIMS This study was conducted to determine whether atenolol was able to decrease BP level and mitigate BP increase during dynamic resistance exercise performed at three different intensities in hypertensives. METHODS Ten essential hypertensives (systolic/diastolic BP between 140/90 and 160/105 mmHg) were blindly studied after 6 weeks of placebo and atenolol. In each phase, volunteers executed, in a random order, three protocols of knee-extension exercises to fatigue: (i) one set at 100% of 1 RM; (ii) three sets at 80% of 1 RM; and (iii) three sets at 40% of 1 RM. Intra-arterial radial blood pressure was measured throughout the protocols. RESULTS Atenolol decreased systolic BP maximum values achieved during the three exercise protocols (100% = 186 +/- 4 vs. 215 +/- 7, 80% = 224 +/- 7 vs. 247 +/- 9 and 40% = 223 +/- 7 vs. 252 +/- 16 mmHg, P < 0.05). Atenolol also mitigated an increase in systolic BP in the first set of exercises (100% = +38 +/- 5 vs. +54 +/- 9; 80% = +68 +/- 11 vs. +84 +/- 13 and 40% = +69 +/- 7 vs. +84 +/- 14, mmHg, P < 0.05). Atenolol decreased diastolic BP values and mitigated its increase during exercise performed at 100% of 1 RM (126 +/- 6 vs. 145 +/- 6 and +41 +/- 6 vs. +52 +/- 6, mmHg, P < 0.05), but not at the other exercise intensities. CONCLUSIONS Atenolol was effective in both reducing systolic BP maximum values and mitigating BP increase during resistance exercise performed at different intensities in hypertensive subjects.

Anabolic steroid associated to physical training induces deleterious cardiac effects

DO CARMO, E. C., T. FERNANDES, D. KOIKE, N. D. DA SILVA JR., K. C. MATTOS, K. T. ROSA, D. BARRETTI, S. F. S. MELO, R. B. WICHI, M. C. C. IRIGOYEN, and E. M. DE OLIVEIRA. Anabolic Steroid Associated to Physical Training Induces Deleterious Cardiac Effects. Med. Sci. Sports Exerc., Vol. 43, No. 10, pp. 1836-1848, 2011. Purpose: Cardiac aldosterone might be involved in the deleterious effects of nandrolone decanoate (ND) on the heart. Therefore, we investigated the involvement of cardiac aldosterone, by the pharmacological block of AT1 or mineralocorticoid receptors, on cardiac hypertrophy and fibrosis. Methods: Male Wistar rats were randomized into eight groups (n = 14 per group): Control (C), nandrolone decanoate (ND), trained (T), trained ND (TND), ND + losartan (ND + L), trained ND + losartan (TND + L), ND + spironolactone (ND + S), and trained ND + spironolactone (TND + S). ND (10 mg.kg(-1).wk(-1)) was administered during 10 wk of swimming training (five times per week). Losartan (20 mg.kg(-1).d(-1)) and spironolactone (10 mg.kg(-1).d(-1)) were administered in drinking water. Results: Cardiac hypertrophy was increased 10% by using ND and 17% by ND plus training (P < 0.05). In both groups, there was an increase in the collagen volumetric fraction (CVF) and cardiac collagen type III expression (P < 0.05). The ND treatment increased left ventricle-angiotensin-converting enzyme I activity, AT1 receptor expression, aldosterone synthase (CYP11B2), and 11-beta hydroxysteroid dehydrogenase 2 (11 beta-HSD2) gene expression and inflammatory markers, TGF beta and osteopontin. Both losartan and spironolactone inhibited the increase of CVF and collagen type III. In addition, both treatments inhibited the increase in left ventricle-angiotensin-converting enzyme I activity, CYP11B2, 11 beta-HSD2, TGF beta, and osteopontin induced by the ND treatment. Conclusions: We believe this is the first study to show the effects of ND on cardiac aldosterone. Our results suggest that these effects may be associated to TGF beta and osteopontin. Thus, we conclude that the cardiac aldosterone has an important role on the deleterious effects on the heart induced by ND.

Finger blood pressure during leg resistance exercise

Blood pressure (BP) assessment during resistance exercise can be useful to avoid high BP, reducing cardiovascular risk, especially in hypertensive individuals. However, non-invasive accurate technique for this purpose is not available. The aim of this study was to compare finger photoplethysmographic (FPP) and intra-arterial BP values and responses during resistance exercise. Eight non-medicated hypertensive subjects (5 males, 30-60 years) were evaluated during pre-exercise resting period and during three sets of the knee extension exercise performed at 80% of 1RM until fatigue. BP was measured simultaneously by FPP and intra-arterial methods. Data are mean +/- SD. Systolic BP was significantly higher with FPP than with intra-arterial: at pre-exercise (157 +/- 13 vs. 152 +/- 10 mmHg; p < 0.01) and the mean (202 +/- 29 vs. 198 +/- 26 mmHg; p < 0.01), and the maximal (240 +/- 26 vs. 234 +/- 16 mmHg; p < 0.05) values achieved during exercise. The increase in systolic BP during resistance exercise was similar between FPP and intra-arterial (+ 73 +/- 29 vs. + 71 +/- 18 mmHg; p = 0.59). Diastolic BP values and increases were lower with FPP. In conclusion, FPP provides similar values of BP increment during resistance exercise than intra-arterial method. However, it overestimates by 2.6 +/- 6.1% the maximal systolic BP achieved during this mode of exercise and underestimates by 8.8 +/- 5.8% the maximal diastolic BP.

Weight loss associated with exercise training restores ventilatory efficiency in obese children

The purpose of this study was to test the hypothesis that in obese children: 1) Ventilatory efficiency (VentE) is decreased during graded exercise; and 2) Weight loss through diet alone (D) improves VentE, and 3) diet associated with exercise training (DET) leads to greater improvement in VentE than by D. Thirty-eight obese children (10 +/- 0.2 years; BMI > 95(th) percentile) were randomly divided into two Study groups: D (n=17; BMI = 30 +/- 1 kg/m(2)) and DET (n = 21; 28 +/- 1 kg/m(2)). Ten lean children were included in a control group (10 +/- 0.3 years; 17 +/- 0.5 kg/m(2)). All children performed maximal treadmill testing with respiratory gas analysis (breath-by-breath) to determine the ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO(2) peak). VentE was determined by the VE/VCO(2) method at VAT. Obese children showed lower VO(2) peak and lower VentE than controls (p < 0.05). After interventions, all obese children reduced body weight (p < 0.05). D group did not improve in terms of VO(2) peak or VentE (p > 0.05). In contrast, the DET group showed increased VO(2) peak (p = 0.01) and improved VentE(Delta VE/VCO(2) = -6.1 +/- 0.9; p = 0.01). VentE is decreased in obese children, where weight loss by means of DET, but not D alone, improves VentE and cardiorespiratory fitness during graded exercise.

Neuromuscular activity during bench press exercise performed with and without the preexhaustion method

Brennecke, A, Guimaraees, TM, Leone, R, Cadarci, M, Mochizuki, L, Simao, R, Amadio, AC, and Serrao, J. Neuromuscular activity during bench press exercise performed with and without the preexhaustion method. J Strength Cond Res 23(7): 1933-1940, 2009-The purpose of the present study was to investigate the effects of exercise order on the tonic and phasic characteristics of upper-body muscle activity during bench press exercise in trained subjects. The preexhaustion method involves working a muscle or a muscle group combining a single-joint exercise immediately followed by a multi-joint exercise (e. g., flying exercise followed by bench press exercise). Twelve subjects performed 1 set of bench press exercises with and without the preexhaustion method following 2 protocols (P1-flying before bench press; P2-bench press). Both exercises were performed at a load of 10 repetition maximum (10RM). Electromyography (EMG) sampled at 1 kHz was recorded from the pectoralis major (PM), anterior deltoid (DA), and triceps brachii (TB). Kinematic data (60 Hz) were synchronized to define upward and downward phases of exercise. No significant (p > 0.05) changes were seen in tonic control of PM and DA muscles between P1 and P2. However, TB tonic aspect of neurophysiologic behavior of motor units was significantly higher (p < 0.05) during P1. Moreover, phasic control of PM, DA, and TB muscles were not affected (p > 0.05). The kinematic pattern of movement changed as a result of muscular weakness in P1. Angular velocity of the right shoulder performed during the upward phase of the bench press exercise was significantly slower (p < 0.05) during P1. Our results suggest that the strategies set by the central nervous system to provide the performance required by the exercise are held constant throughout the exercise, but the tonic aspects of the central drive are increased so as to adapt to the progressive occurrence of the neuromuscular fatigue. Changes in tonic control as a result of the muscular weakness and fatigue can cause changes in movement techniques. These changes may be related to limited ability to control mechanical loads and mechanical energy transmission to joints and passive structures.

Cardiac anti-remodelling effect of aerobic training is associated with a reduction in the calcineurin/NFAT signalling pathway in heart failure mice

Cardiomyocyte hypertrophy occurs in response to a variety of physiological and pathological stimuli. While pathological hypertrophy in heart failure is usually coupled with depressed contractile function, physiological hypertrophy associates with increased contractility. In the present study, we explored whether 8 weeks of moderate intensity exercise training would lead to a cardiac anti-remodelling effect in an experimental model of heart failure associated with a deactivation of a pathological (calcineurin/NFAT, CaMKII/HDAC) or activation of a physiological (Akt-mTOR) hypertrophy signalling pathway. The cardiac dysfunction, exercise intolerance, left ventricle dilatation, increased heart weight and cardiomyocyte hypertrophy from mice lacking alpha(2A) and alpha(2C) adrenoceptors (alpha(2A)/alpha(2C)ARKO mice) were associated with sympathetic hyperactivity induced heart failure. The relative contribution of Ca(2+)-calmodulin high-affinity (calcineurin/NFAT) and low-affinity (CaMKII/HDAC) targets to pathological hypertrophy of alpha(2A)/alpha(2C)ARKO mice was verified. While nuclear calcineurin B, NFATc3 and GATA-4 translocation were significantly increased in alpha(2A)/alpha(2C)ARKO mice, no changes were observed in CaMKII/HDAC activation. As expected, cyclosporine treatment decreased nuclear translocation of calcineurin/NFAT in alpha(2A)/alpha(2C)ARKO mice, which was associated with improved ventricular function and a pronounced anti-remodelling effect. The Akt/mTOR signalling pathway was not activated in alpha(2A)/alpha(2C)ARKO mice. Exercise training improved cardiac function and exercise capacity in alpha(2A)/alpha(2C)ARKO mice and decreased heart weight and cardiomyocyte width paralleled by diminished nuclear NFATc3 and GATA-4 translocation as well as GATA-4 expression levels. When combined, these findings support the notion that deactivation of calcineurin/NFAT pathway-induced pathological hypertrophy is a preferential mechanism by which exercise training leads to the cardiac anti-remodelling effect in heart failure.

Post-concurrent exercise hemodynamics and cardiac autonomic modulation

Concurrent training is recommended for health improvement, but its acute effects on cardiovascular function are not well established. This study analyzed hemodynamics and autonomic modulation after a single session of aerobic (A), resistance (R), and concurrent (A + R) exercises. Twenty healthy subjects randomly underwent four sessions: control (C:30 min of rest), aerobic (A:30 min, cycle ergometer, 75% of VO(2) peak), resistance (R:6 exercises, 3 sets, 20 repetitions, 50% of 1 RM), and concurrent (AR: A + R). Before and after the interventions, blood pressure (BP), heart rate (HR), cardiac output (CO), and HR variability were measured. Systolic BP decreased after all the exercises, and the greatest decreases were observed after the A and AR sessions (-13 +/- 1 and -11 +/- 1 mmHg, respectively, P < 0.05). Diastolic BP decreased similarly after all the exercises, and this decrease lasted longer after the A session. CO also decreased similarly after the exercises, while systemic vascular resistance increased after the R and AR sessions in the recovery period (+4.0 +/- 1.7 and +6.3 +/- 1.9 U, respectively, P < 0.05). Stroke volume decreased, while HR increased after the exercises, and the greatest responses were observed after the AR session (SV, A = -14.6 +/- 3.6, R = -22.4 +/- 3.5 and AR = -23.4 +/- 2.4 ml; HR, A = +13 +/- 2, R = +15 +/- 2 vs. AR = +20 +/- 2 bpm, P < 0.05). Cardiac sympathovagal balance increased after the exercises, and the greatest increase was observed after the AR session (A = +0.7 +/- 0.8, R = +1.0 +/- 0.8 vs. AR = +1.2 +/- 0.8, P < 0.05). In conclusion, the association of aerobic and resistance exercises in the same training session did not potentiate postexercise hypotension, and increased cardiac sympathetic activation during the recovery period.

Clinic and ambulatory blood pressure responses after resistance exercise

Queiroz, ACC, Gagliardi, JFL, Forjaz, CLM, and Rezk, CC. Clinic and ambulatory blood pressure responses after resistance exercise. J Strength Cond Res 23(2): 571-578, 2009-This study investigated clinic and ambulatory blood pressure (BP) responses after a single bout of low-intensity resistance exercise in normotensive subjects. Fifteen healthy subjects underwent 2 experimental sessions: control-40 minutes of seated rest, and exercise-6 resistance exercises, with 3 sets of as many repetitions as possible until moderate fatigue, with an intensity of 50% of 1-repetition maximum (1RM). Before and for 60 minutes after interventions, clinic BP was measured by auscultatory and oscillometric methods. Postintervention ambulatory BP levels were also measured for 24 hours. In comparison with preintervention values, clinic systolic BP, as measured by the auscultatory method, did not change in the control group, but it decreased after exercise (-3.7 +/- 1.6 mm Hg, p < 0.05). Diastolic and mean BP levels increased after intervention in the control group (+3.4 +/- 1.0 and +3.0 +/- 0.8 mm Hg, respectively, p, 0.05) and decreased in the exercise group (-3.6 +/- 1.7 and -3.4 +/- 1.4 mm Hg, respectively, p < 0.05). Systolic and mean oscillometric BP levels did not change after interventions either in the control or exercise sessions, whereas diastolic BP increased after intervention in the control group (+5.0 +/- 1.7 mm Hg, p < 0.05) but not change after exercise. Ambulatory BP behaviors after interventions were similar in the control and exercise sessions. Significant and positive correlations were observed between preexercise values and postexercise clinic and ambulatory BP decreases. In conclusion, in the whole sample, a single bout of low-intensity resistance exercise decreased postexercise BP under clinic, but not ambulatory, conditions. However, considering individual responses, postexercise clinic and ambulatory hypotensive effects were greater in subjects with higher preexercise BP levels.

Moderate exercise training decreases aortic superoxide production in myocardial infarcted rats

Myocardial infarction (MI) has been associated with increases in reactive oxygen species (ROS). Exercise training (ET) has been shown to exert positive modulations on vascular function and the purpose of the present study was to investigate the effect of moderate ET on the aortic superoxide production index, NAD(P)H oxidase activity, superoxide dismutase activity and vasomotor response in MI rats. Aerobic ET was performed during 11 weeks. Myocardial infarction significantly diminished maximal exercise capacity, and increased vasoconstrictory response to norepinephrine, which was related to the increased activity of NAD(P)H oxidase and basal superoxide production. On the other hand, ET normalized the superoxide production mostly due to decreased NAD(P)H oxidase activity, although a minor SOD effect may also be present. These adaptations were paralleled by normalization in the vasoconstrictory response to norepinephrine. Thus, diminished ROS production seems to be an important mechanism by which ET mediates its beneficial vascular effects in the MI condition.

Post-resistance exercise hypotension in spontaneously hypertensive rats is mediated by nitric oxide

1. Postexercise hypotension (PEH) plays an important role in the non-pharmacological treatment of hypertension. It is characterized by a decrease in blood pressure (BP) after a single bout of exercise in relation to pre-exercise levels. 2. The present study investigated the effect of a single session of resistance exercise, as well as the effect of nitric oxide (NO) and the autonomic nervous system (ANS), in PEH in spontaneously hypertensive rats (SHR). 3. Catheters were inserted into the left carotid artery and left jugular vein of male SHR (n = 37) for the purpose of measuring BP or heart rate (HR) and drug or vehicle administration, respectively. Haemodynamic measurements were made before and after acute resistance exercise. The roles of NO and the ANS were investigated by using N(G)-nitro-L-arginine methyl ester (L-NAME; 15 mg/kg, i.v.) and hexamethonium (20 mg/kg, i.v.) after a session of acute resistance exercise. 4. Acute resistance exercise promoted a pronounced reduction in systolic and diastolic BP (-37 +/- 1 and -8 +/- 1 mmHg, respectively; P < 0.05), which was suppressed after treatment with L-NAME. The reduction in systolic BP caused by exercise (-37 +/- 1 mmHg) was not altered by the administration of hexamethonium (-38 +/- 2 mmHg; P > 0.05). After exercise, the decrease in diastolic BP was greater with hexamethonium (-26 +/- 1 mmHg; P < 0.05) compared with the decrease caused by exercise alone. 5. The results suggest that acute resistance exercise has an important hypotensive effect on SHR and that NO plays a crucial role in this response.

PKC beta II inhibition attenuates myocardial infarction induced heart failure and is associated with a reduction of fibrosis and pro-inflammatory responses

Protein kinase C beta II (PKC beta II) levels increase in the myocardium of patients with end-stage heart failure (HF). Also targeted overexpression of PKC beta II in the myocardium of mice leads to dilated cardiomyopathy associated with inflammation, fibrosis and myocardial dysfunction. These reports suggest a deleterious role of PKC beta II in HF development. Using a post-myocardial infarction (MI) model of HF in rats, we determined the benefit of chronic inhibition of PKC beta II on the progression of HF over a period of 6 weeks after the onset of symptoms and the cellular basis for these effects. Four weeks after MI, rats with HF signs that were treated for 6 weeks with the PKC beta II selective inhibitor (beta IIV5-3 conjugated to TAT(47-57) carrier peptide) (3 mg/kg/day) showed improved fractional shortening (from 21% to 35%) compared to control (TAT(47-57) carrier peptide alone). Formalin-fixed mid-ventricle tissue sections stained with picrosirius red, haematoxylin and eosin and toluidine blue dyes exhibited a 150% decrease in collagen deposition, a two-fold decrease in inflammation and a 30% reduction in mast cell degranulation, respectively, in rat hearts treated with the selective PKC beta II inhibitor. Further, a 90% decrease in active TGF beta 1 and a significant reduction in SMAD2/3 phosphorylation indicated that the selective inhibition of PKC beta II attenuates cardiac remodelling mediated by the TGF-SMAD signalling pathway. Therefore, sustained selective inhibition of PKC beta II in a post-MI HF rat model improves cardiac function and is associated with inhibition of pathological myocardial remodelling.

Adaptations in autonomic function during exercise training in heart failure

Although neurohumoral excitation is the hallmark of heart failure (HF), the mechanisms underlying this alteration are not entirely known. Abnormalities in several systems contribute to neurohumoral excitation in HF, including arterial and cardiopulmonary baroreceptors, central and peripheral chemoreceptors, cardiac chemoreceptors, and central nervous system abnormalities. Exercise intolerance is characteristic of chronic HF, and growing evidence strongly suggests that exercise limitation in patients with chronic HF is not due to elevated filling pressures or inadequate cardiac output during exercise, but instead due to skeletal myopathy. Several lines of evidence suggest that sympathetic excitation contributes to the skeletal myopathy of HF, since sympathetic activity mediates vasoconstriction at rest and during exercise likely restrains muscle blood flow, arteriolar dilatation, and capillary recruitment, leading to underperfused areas of working muscle, and areas of muscle ischemia, release of reactive oxygen species (ROS), and inflammation. Although controversial, either unmyelinated, metabolite-sensitive afferent fibers, and/or myelinated, mechanosensitive afferent fibers in skeletal muscle underlie the exaggerated sympathetic activity in HF. Exercise training has emerged as a unique non-pharmacological strategy for the treatment of HF. Regular exercise improves functional capacity and quality of life, and perhaps prognosis in chronic HF patients. Recent studies have provided convincing evidence that these benefits in chronic HF patients are mediated by significant reduction in central sympathetic outflow as a consequence of improvement in arterial and chemoreflex controls, and correction of central nervous system abnormalities, and increase in peripheral blood flow with reduction in cytokines and increase in mass muscle.