Alpha and beta adrenergic sensitivity in trained and untrained albino rats.

The effects on the blood pressure and heart rate responses of different adrenergic stimulants (norepinephrine, sympathomim, epinephrine and isoproterenol) and blocking agents (phenoxybenzamine and propranolol) were studied in control (N=55) and exercising (N=52) albino rats under anaesthesia. The test rats exercised by regular swimming for 10-14 weeks. Alpha stimulation and beta blocking produced smaller responses while alpha blocking and beta stimulation were followed by greater changes after training as compared with the control animals. The assumption of a modified adrenergic receptor sensitivity could not be substantiated by the results; the observations indicate rather a complex change in the autonomous regulation following regular physical exercise.     

Metabolic and endocrine responses to prolonged exercise in rats under beta 2-adrenergic blockade

The respective roles of allosteric regulators and catecholamines in the control of muscle glycogen breakdown during exercise remain a matter of controversy. This study was designed to reassess the role of the sympathoadrenal system during prolonged exercise in rats. Animals were studied at rest or after treadmill exercise (28 m.min-1; 8% slope) to exhaustion in a control situation or following administration of a specific beta 2-adrenergic receptor antagonist (ICI 118,551, 1 mg.kg-1, i.v.). Running times to exhaustion were 54 and 36 min in control and treated rats, respectively. For the purpose of comparison, another group of control rats was studied after a 36-min exercise bout. The reduction in endurance in treated rats was associated with an impairment in glycogen utilization, as measured by muscle glycogen stores, in soleus muscle but not in superficial vastus lateralis or gastrocnemius lateralis muscles. Utilization of liver glycogen stores was similar in the two groups of animals, but plasma glucose (7 vs. 13 mM) and lactate (4 vs. 7 mM) levels were significantly lower in rats under beta-blockade than in control rats run for 36 min. Plasma free fatty acid and glycerol concentrations were not significantly different between groups. On the other hand, plasma epinephrine concentration was significantly higher in treated rats (13 vs. 5 mM), which might reflect a compensatory increase in adrenal activity. These results suggest that glycogen breakdown during prolonged exercise is under the control of the sympathoadrenal system in predominantly slow-twitch but not in predominantly fast-twitch muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipid peroxidation and scavenger enzymes during exercise: adaptive response to training

This study was designed to determine whether endurance training would influence the production of lipid peroxidation (LI-POX) by-products as indicated by malondialdehyde (MDA) at rest and after an acute exercise run. Additionally, the scavenger enzymes catalase (CAT) and superoxide dismutase (SOD) were examined to determine whether changes in LIPOX are associated with alterations in enzyme activity both at rest and after exercise. Male Sprague-Dawley rats (n = 32) were randomly assigned to either trained or sedentary groups and were killed either at rest or after 20 min of treadmill running. The training program increased oxidative capacity 64% in leg muscle. After exercise, the sedentary group demonstrated increased LIPOX levels in liver and white skeletal muscle, whereas the endurance-trained group did not show increases in LIPOX after exercise. CAT activity was higher in both red and white muscle after exercise in the trained animals. Total SOD activity was unaffected by either acute or chronic exercise. These data suggest that endurance training can result in a reduction in LIPOX levels as indicated by MDA during moderate-intensity exercise. It is possible that activation of the enzyme catalase and the increase in respiratory capacity were contributory factors responsible for regulating LIPOX after training during exercise.     

Effects of chronic and acute exercise on cardiovascular beta-adrenergic responses.

beta-Adrenergic receptor density and responsiveness may be increased in experimental animals by physical conditioning, and the opposite effects have been observed after a single bout of exercise. To determine whether the chronic and acute effects of exercise include similar alterations in cardiovascular function in humans, we characterized heart rate, blood pressure, and distal lower extremity blood flow responses to graded-dose isoproterenol infusion in 15 young healthy subjects before and after exercise training and with and without a single preceding bout of prolonged exercise of either low or high intensity (61 +/- 1 or 82 +/- 1% maximal heart rate). VO2max was increased 18% after exercise training (43.2 +/- 2.7 to 51.1 +/- 3.3 ml.kg-1.min-1; P less than 0.001). Despite a concomitant fall in resting heart rate (59 +/- 3 to 50 +/- 2 beats/min; P less than 0.001), chronotropic and lower extremity blood flow responses to isoproterenol remained unchanged. Similarly, 1 h of acute high-intensity treadmill exercise altered baseline heart rate (58 +/- 4 to 74 +/- 5 beats/min; P less than 0.02), but neither low- nor high-intensity acute exercise influenced heart rate or lower extremity blood flow responses to isoproterenol. In contrast, the systolic pressure response to isoproterenol was blunted after high- but not low-intensity prolonged exercise (P less than 0.02). These data indicate that cardiac chronotropic (primarily beta 1) and vascular (beta 2) adrenergic agonist responses are not altered in humans by training or acute exercise. The systolic blood pressure response to beta-adrenergic stimulation is decreased by a single bout of high-intensity prolonged exercise by mechanisms that remain to be defined.     

Forearm endurance training attenuates sympathetic nerve response to isometric handgrip in normal humans.

Recent evidence indicates that muscle ischemia and activation of the muscle chemoreflex are the principal stimuli to sympathetic nerve activity (SNA) during isometric exercise. We postulated that physical training would decrease muscle chemoreflex stimulation during isometric exercise and thereby attenuate the SNA response to exercise. We investigated the effects of 6 wk of unilateral handgrip endurance training on the responses to isometric handgrip (IHG: 33% of maximal voluntary contraction maintained for 2 min). In eight normal subjects the right arm underwent exercise training and the left arm sham training. We measured muscle SNA (peroneal nerve), heart rate, and blood pressure during IHG before vs. after endurance training (right arm) and sham training (left arm). Maximum work to fatigue (an index of training efficacy) was increased by 1,146% in the endurance-trained arm and by only 40% in the sham-trained arm. During isometric exercise of the right arm, SNA increased by 111 +/- 27% (SE) before training and by only 38 +/- 9% after training (P less than 0.05). Endurance training did not significantly affect the heart rate and blood pressure responses to IHG. We also measured the SNA response to 2 min of forearm ischemia after IHG in five subjects. Endurance training also attenuated the SNA response to postexercise forearm ischemia (P = 0.057). Sham training did not significantly affect the SNA responses to IHG or forearm ischemia. We conclude that endurance training decreases muscle chemoreflex stimulation during isometric exercise and thereby attenuates the sympathetic nerve response to IHG.     

Endurance training restores peritoneal macrophage function in post-MI congestive heart failure rats.

Congestive heart failure (CHF) induces a state of immune activation, and peritoneal macrophages (M phi s) may play an important role in the development and progression of one such condition. Moderate endurance training modulates peritoneal M phi function. We evaluated the effect of endurance training on different stages of the phagocytic process and in the production of interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) after LPS stimulation. Either ligation of the left coronary artery or Sham operations were performed in adult Wistar rats. After 4 wk, control (Sham operated) and MI (ligation of the left coronary artery) animals were randomly assigned to either a sedentary (Sham-operated sedentary, n = 7 and MI sedentary, n = 10) or a trained group (Sham-operated trained, n = 8 and MI trained, n = 8). Trained rats ran on a treadmill (0% grade at 13-20 m/min) for 60 min/day, 5 days/wk, for 8-10 wk, whereas sedentary rats had only limited activity. Training increased maximal oxygen uptake normalized for body weight (ml.kg(-1).min(-1)), as well as skeletal muscle citrate synthase maximal activity, when compared with sedentary groups. The resident and total cell number, the chemotaxis index, and the production of TNF-alpha stimulated by LPS were significantly higher in the MI sedentary group when compared with the Sham sedentary group. Moderate endurance training reversed these alterations promoted by post-MI. These results demonstrate that moderate intensity exercise training modulates peritoneal M phi function and induces beneficial metabolic effects in rats with post-MI CHF.     

Effects of training on glucose metabolism of gluconeogenesis-inhibited short-term-fasted rats

To evaluate the effects of endurance training on gluconeogenesis and blood glucose homeostasis, trained as well as untrained short-term-fasted rats were injected with mercaptopicolinic acid (MPA), a gluconeogenic inhibitor, or the injection vehicle. Glucose kinetics were assessed by primed-continuous venous infusion of [U-14C]- and [6-3H]glucose at rest and during submaximal exercise at 13.4 m/min on level grade. Arterial blood was sampled for the determination of blood glucose and lactate concentrations and specific activities. In resting untrained sham-injected rats, blood glucose and lactate were 7.6 +/- 0.2 and 1.3 +/- 0.1 mM, respectively; glucose rate of appearance (Ra) was 71.1 +/- 12.1 mumol.kg-1.min-1. MPA treatment lowered blood glucose, raised lactate, and decreased glucose Ra. Trained animals had significantly higher glucose Ra at rest and during exercise. At rest, trained MPA-treated rats had lower blood glucose, higher blood lactate, and similar glucose Ra and disappearance rates (Rd) than trained sham-injected animals. Exercising sham-injected untrained animals had increased blood glucose and glucose Ra compared with rest. Exercising trained sham-injected rats had increased blood glucose and glucose Ra and Rd but no change in blood lactate compared with untrained sham-injected animals. In the trained animals during exercise, MPA treatment increased blood lactate and decreased blood glucose and glucose Ra and Rd. There was no measurable glucose recycling in trained or untrained MPA-treated animals either at rest or during submaximal exercise. There was no difference in running time to exhaustion between trained and untrained MPA-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phosphorus-31 nuclear magnetic resonance study on the effects of endurance training in rat skeletal muscle

To evaluate changes in muscle energetics following endurance training, we measured phosphorus-31 nuclear magnetic resonance (31P NMR) spectra on rat muscle in vivo before and after training in the same animals. The endurance training lasted for 3 months. The 31P NMR spectra were obtained serially at rest, during exercise by electrical stimulation, and during recovery. Intramuscular phosphocreatine (PCr), inorganic phosphate (P(i)), adenosine 5'-triphosphate (ATP) and pH were determined from the NMR spectra. The ratio of PCr:(PCR + P(i) at rest showed no difference between the trained and control groups even after 3 months of training. During exercise, however, this ratio was significantly higher in the trained group than in the control group. The ratio also recovered more rapidly after exercise in the trained group. The intramuscular pH decreased slightly by approximately 0.1 pH unit during exercise but did not show a significant difference between the groups. These results indicated that endurance training of 3 months duration improved the ATP supply system in the muscle. They also demonstrated that 31P NMR is a potent method for evaluating the effects of training in the same individuals.     

科素亚对长期大强度运动所致大鼠心脏纤维化的预防作用

目的:研究血管紧张素Ⅱ1型受体拮抗剂科素亚对长期大强度运动所致心脏纤维化的预防作用。方法:48只雄性Wistar大鼠随机分为4组:对照组,科素亚处理的对照组,运动组,运动+科素亚处理组。运动组大鼠给予16周大强度运动,科素亚处理的大鼠每天训练前口服科素亚每次(50毫克/公斤/天)。通过计算心系数和观察心脏的组织形态学评估和比较各组大鼠心脏肥大的程度,免疫印迹法检测和比较各组大鼠4个心腔内转化生长因子-β1、纤维连接蛋白1、基质金属蛋白酶-2、I型胶原蛋白和III型胶原蛋白的蛋白表达水平。结果:长期大强度运动可造成大鼠左心室心脏壁肥大和右心室胶原沉积,心房和右心室的主要纤维化生物标志物的蛋白表达水平显著增加。科素亚预处理能够减少主要纤维化生物标志物TGF-β1、FIBROECTIN-1、MMP-2、TIMP-1、COLLAGEN-I、COLLAGEN-III表达水平,但不能完全改变心脏重量与体重比值增大的状态。结论:科素亚可部分预防耐力运动训练所致的心脏纤维化,但不能彻底改善心脏肥大。     

Effect of Voluntary Ethanol Consumption Combined with Testosterone Treatment on Cardiovascular Function in Rats: Influence of Exercise Training

This study evaluated the effects of voluntary ethanol consumption combined with testosterone treatment on cardiovascular function in rats. Moreover, we investigated the influence of exercise training on these effects. To this end, male rats were submitted to low-intensity training on a treadmill or kept sedentary while concurrently being treated with ethanol for 6 weeks. For voluntary ethanol intake, rats were given access to two bottles, one containing ethanol and other containing water, three 24-hour sessions per week. In the last two weeks (weeks 5 and 6), animals underwent testosterone treatment concurrently with exercise training and exposure to ethanol. Ethanol consumption was not affected by either testosterone treatment or exercise training. Also, drug treatments did not influence the treadmill performance improvement evoked by training. However, testosterone alone, but not in combination with ethanol, reduced resting heart rate. Moreover, combined treatment with testosterone and ethanol reduced the pressor response to the selective α₁-adrenoceptor agonist phenylephrine. Treatment with either testosterone or ethanol alone also affected baroreflex activity and enhanced depressor response to acetylcholine, but these effects were inhibited when drugs were coadministrated. Exercise training restored most cardiovascular effects evoked by drug treatments. Furthermore, both drugs administrated alone increased pressor response to phenylephrine in trained animals. Also, drug treatments inhibited the beneficial effects of training on baroreflex function. In conclusion, the present results suggest a potential interaction between toxic effects of testosterone and ethanol on cardiovascular function. Data also indicate that exercise training is an important factor influencing the effects of these substances.     

Effects of endurance training and acute exhaustive exercise on antioxidant defense mechanisms in rat heart

We investigated whether 8-week treadmill training strengthens antioxidant enzymes and decreases lipid peroxidation in rat heart. The effects of acute exhaustive exercise were also investigated. Male rats (Rattus norvegicus, Sprague-Dawley strain) were divided into trained and untrained groups. Both groups were further divided equally into two groups where the rats were studied at rest and immediately after exhaustive exercise. Endurance training consisted of treadmill running 1.5 h day(-1), 5 days week(-1) for 8 weeks. For acute exhaustive exercise, graded treadmill running was conducted. Malondialdehyde level in heart tissue was not affected by acute exhaustive exercise in untrained and trained rats. The activities of glutathione peroxidase and glutathione reductase enzymes decreased by both acute exercise and training. Glutathione S-transferase and catalase activities were not affected. Total and non-enzymatic superoxide scavenger activities were not affected either. Superoxide dismutase activity decreased by acute exercise in untrained rats; however, this decrease was not observed in trained rats. Our results suggested that rat heart has sufficient antioxidant enzyme capacity to cope with exercise-induced oxidative stress, and adaptive changes in antioxidant enzymes due to endurance training are limited.     

Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts

Cardiac myocytes produce nitric oxide (NO). We studied the effects of intense exercise on the expression of NO synthase (NOS) and the tissue level of nitrite (NO(2)(-))/nitrate (NO(3)(-)) (i.e., NOx), which are stable end products of NO in the heart. Rats ran on a treadmill for 45 min. Immediately after this exercise, the heart was quickly removed. Control rats remained at rest during the same 45-min period. The mRNA level of endothelial NOS (eNOS) in the heart was markedly lower in the exercised rats than in the control rats. Western blot analysis confirmed downregulation of eNOS protein in the heart after exercise. Tissue NOx level in the heart was significantly lower in the exercised rats than in the control rats. The present study revealed for the first time that production of NO in the heart is decreased by intense exercise. Because NO attenuates positive inotropic and chronotropic responses to beta(1)-adrenergic stimulation in the heart, the decrease in cardiac production of NO by intense exercise may contribute to the acceleration of increase in myocardial contractility and heart rate during intense exercise.     

Glucocorticoid receptor activation during exercise in muscle

This investigation was undertaken to evaluate whether endurance running of the type known to retard the muscle atrophy associated with glucocorticoid excess inhibits activation of glucocorticoid-receptor complexes to a DNA binding state. Female adrenalectomized rats received an injection (50 microCi/100 g body wt ip) of [3H]triamcinolone acetonide and remained sedentary or were immediately exercised by endurance running at 23 m/min for up to 90 min. Receptor activation, as quantified by binding to DNA-cellulose, steadily increased from 10-20% of the receptors capable of binding DNA in uninjected controls to 25-45% by 5 min and to 53-80% by 90 min after receiving the hormone in all muscles studied (fast-twitch red vastus lateralis, fast-twitch white vastus lateralis, slow-twitch soleus, mixed gastrocnemius, and heart). Exercise did not influence the time-course changes in percent activation. When activation was determined from changes in the conformational state of the receptor as measured by diethylaminoethyl-cellulose anion exchange chromatography, there was a similar time-dependent formation of activated receptor forms in all muscle types. However, exercise did not inhibit or delay the appearance of the activated receptor from the unactivated state. These results indicate that glucocorticoid receptor activation occurs at a rate that is independent of both fiber type and delivery of steroid to working muscles during exercise. If exercise alters receptor activation, a longer time period, beyond 90 min of running, or even additional training may be needed for inhibition to be expressed.     

Exercise training and beta-blocker treatment ameliorate age-dependent impairment of beta-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation

Cardiac beta-adrenergic receptor (beta-AR) signaling and left ventricular (LV) responses to beta-AR stimulation are impaired with aging. It is shown that exercise and beta-AR blockade have a favorable effect on cardiac and vascular beta-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on beta-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise (12 wk treadmill training), metoprolol (250 mg.kg(-1).day(-1) for 4 wk), and exercise plus metoprolol treatment protocols. Ten male Wistar-Kyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprolol-treated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to beta-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane beta-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac beta-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-protein-receptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of beta-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and beta-AR blockade can similarly ameliorate beta-AR signaling in the aged heart, leading to improved beta-AR responsiveness and corresponding LV inotropic reserve.     

Training does not protect against exhaustive exercise-induced lactate transport capacity alterations

The effects of endurance training on lactate transport capacity remain controversial. This study examined whether endurance training 1) alters lactate transport capacity, 2) can protect against exhaustive exercise-induced lactate transport alteration, and 3) can modify heart and oxidative muscle monocarboxylate transporter 1 (MCT1) content. Forty male Wistar rats were divided into control (C), trained (T), exhaustively exercised (E), and trained and exercised (TE) groups. Rats in the T and TE groups ran on a treadmill (1 h/day, 5 days/wk at 25 m/min, 10% incline) for 5 wk; C and E were familiarized with the exercise task for 5 min/day. Before being killed, E and TE rats underwent exhaustive exercise (25 m/min, 10% grade), which lasted 80 and 204 min, respectively (P < 0.05). Although lactate transport measurements (zero-trans) did not differ between groups C and T, both E and TE groups presented an apparent loss of protein saturation properties. In the trained groups, MCT1 content increased in soleus (+28% for T and +26% for TE; P < 0.05) and heart muscle (+36% for T and +33% for TE; P < 0.05). Moreover, despite the metabolic adaptations typically observed after endurance training, we also noted increased lipid peroxidation byproducts after exhaustive exercise. We concluded that 1) endurance training does not alter lactate transport capacity, 2) exhaustive exercise-induced lactate transport alteration is not prevented by training despite increased MCT1 content, and 3) exercise-induced oxidative stress may enhance the passive diffusion responsible for the apparent loss of saturation properties, possibly masking lactate transport regulation.     

Effect of cocaine on exercise endurance and glycogen use in rats

To determine the effects of cocaine on exercise endurance, male rats were injected intraperitoneally with cocaine (20 mg/kg body wt) or saline and then run to exhaustion 20 min later at 22 m/min and 15% grade. Saline-injected animals ran 74.9 +/- 16.5 (SD) min, whereas cocaine-treated rats ran only 29 +/- 11.6 min. The drug had no effect on resting blood glucose or lactate levels, nor did it affect resting glycogen levels in liver or red and white vastus muscle. However, it did reduce resting soleus glycogen content by 30%. During exercise liver and soleus glycogen depletion occurred at the same rate in saline- and cocaine-treated animals. In contrast, the rate of glycogen depletion during exercise in red and white vastus was markedly increased in cocaine-treated rats with a corresponding elevation in blood lactate (12 vs. only 5 mM in saline group) at exhaustion. These data suggest that cocaine administration (20 mg/kg) before submaximal exercise dramatically alters glycogen metabolism during exercise, and this effect has a negative impact on exercise endurance.     

Effect of contractile activity on rat skeletal muscle beta-adrenoceptor properties

The effect of fiber type and endurance exercise training on skeletal muscle beta-adrenoceptor properties were assessed using a direct radioligand binding technique. Six separate muscles, composed of a variety of different fiber types, were examined in treadmill trained and sedentary rats. In trained animals, sarcolemmal preparations from heart and slow twitch soleus muscle exhibited a significantly greater receptor concentration than membranes from white fast twitch glycolytic fibers of the vastus lateralis. No significant changes were observed between trained and sedentary rat muscle beta-adrenoceptor density (beta max, fmole/mg protein) or affinity (Kd, nM) within each muscle type, despite significantly increased myocardial/body weight ratios and skeletal muscle enzyme adaptations associated with the exercise program. These results suggest that muscle beta-adrenoceptor properties may be influenced in part by the motor nerve innervation to that muscle, and are further discussed with respect to a possible relationship between exercise intensity and receptor regulation.     

Sympathetic adaptations to one-legged training.

The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P < 0.01). At rest, heart rate decreased from 77 +/- 3 to 71 +/- 6 beats/min (P < 0.01) with no significant changes in MAP (91 +/- 7 to 91 +/- 11 mmHg) and MSNA (29 +/- 3 to 28 +/- 1 bursts/min). During exercise, both heart rate and MAP were lower after training (108 +/- 5 to 96 +/- 5 beats/min and 132 +/- 8 to 119 +/- 4 mmHg, respectively, during the third minute of exercise; P < 0.01). MSNA decreased similarly from rest during the first 2 min of exercise both before and after training. However, MSNA was significantly less during the third minute of exercise after training (32 +/- 2 to 22 +/- 3 bursts/min; P < 0.01). This training effect on MSNA remained when MSNA was expressed as bursts per 100 heartbeats. Responses to exercise in five untrained control subjects were not different at 0 and 6 wk. These results demonstrate that exercise training prolongs the decrease in MSNA during upright leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training.     

Regulation of mitochondrial uncoupling respiration during exercise in rat heart: role of reactive oxygen species (ROS) and uncoupling protein 2

The physiological significance of cardiac mitochondrial uncoupling protein 2 (UCP2)-mediated uncoupling respiration in exercise is unknown. In the current study, mitochondrial respiratory function, UCP2 mRNA level, UCP2-mediated respiration (UCR), and reactive oxygen species (ROS) generation, as well as manganese superoxide dismutase (MnSOD) activity were determined in rat heart with or without endurance training after an acute bout of exercise of different duration. In the untrained rats, state 4 respiration and UCR-independent respiration rates were progressively increased with exercise time and were 64 and 70% higher, respectively, than resting rate at 150 min, whereas UCR was elevated by 86% with no significant change in state 3 respiration. UCP2 mRNA level showed a 5- and 4-fold increase, respectively, after 45 and 90 min of exercise, but returned to resting level at 120 and 150 min. Mitochondrial ROS production and membrane potential (Deltapsi) increased progressively until 120 min, followed by a decrease to the resting level at 150 min. MnSOD mRNA abundance showed a 2-fold increase at 120 min but MnSOD activity did not change with exercise. Training significantly increased mitochondrial ATP synthetase activity, ADP to oxygen consumption (P/O) ratio, respiratory control ratio, and MnSOD activity, whereas exercise-induced state 4 respiration, UCR, ROS production, and Deltapsi were attenuated in the trained rats. We conclude that (1) UCP2 mRNA expression and activity in rat heart can be upregulated during prolonged exercise, which may reduce cross-membrane Deltapsi and thus ROS production; and (2) endurance training can blunt exercise-induced UCP2 and UCR, and improve mitochondrial efficiency of oxidative phosphorylation due to increased removal of ROS.     

Cardiac vagal modulation of heart rate during prolonged submaximal exercise in animals with healed myocardial infarctions: effects of training

The present study investigated the effects of long-duration exercise on heart rate variability [as a marker of cardiac vagal tone (VT)]. Heart rate variability (time series analysis) was measured in mongrel dogs (n = 24) with healed myocardial infarctions during 1 h of submaximal exercise (treadmill running at 6.4 km/h at 10% grade). Long-duration exercise provoked a significant (ANOVA, all P < 0.01, means +/- SD) increase in heart rate (1st min, 165.3 +/- 15.6 vs. last min, 197.5 +/- 21.5 beats/min) and significant reductions in high frequency (0.24 to 1.04 Hz) power (VT: 1st min, 3.7 +/- 1.5 vs. last min, 1.0 +/- 0.9 ln ms(2)), R-R interval range (1st min, 107.9 +/- 38.3 vs. last min, 28.8 +/- 13.2 ms), and R-R interval SD (1st min, 24.3 +/- 7.7 vs. last min 6.3 +/- 1.7 ms). Because endurance exercise training can increase cardiac vagal regulation, the studies were repeated after either a 10-wk exercise training (n = 9) or a 10-wk sedentary period (n = 7). After training was completed, long-duration exercise elicited smaller increases in heart rate (pretraining: 1st min, 156.0 +/- 13.8 vs. last min, 189.6 +/- 21.9 beats/min; and posttraining: 1st min, 149.8 +/- 14.6 vs. last min, 172.7 +/- 8.8 beats/min) and smaller reductions in heart rate variability (e.g., VT, pretraining: 1st min, 4.2 +/- 1.7 vs. last min, 0.9 +/- 1.1 ln ms(2); and posttraining: 1st min, 4.8 +/- 1.1 vs. last min, 2.0 +/- 0.6 ln ms(2)). The response to long-duration exercise did not change in the sedentary animals. Thus the heart rate increase that accompanies long-duration exercise results, at least in part, from reductions in cardiac vagal regulation. Furthermore, exercise training attenuated these exercise-induced reductions in heart rate variability, suggesting maintenance of a higher cardiac vagal activity during exercise in the trained state.