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Exercise training lowers resting renal but not cardiac sympathetic activity in humans.

Endurance exercise training has previously been shown to reduce the plasma concentration of norepinephrine. Whether reduction in sympathetic activity is responsible for the blood pressure-lowering effects of exercise training is unknown. Using a radiotracer technique, we measured resting total, cardiac, and renal norepinephrine spillover to plasma in eight habitually sedentary healthy normotensive men (aged 36 +/- 3 years, mean +/- SEM) after 1 month of regular exercise and 1 month of sedentary activity, performed in a randomized order. One month of bicycle exercise 3 times/wk (40 minutes at 60-70% maximum work capacity) reduced resting blood pressure by 8/5 mm Hg (p less than 0.01) and increased maximum oxygen consumption by 15% (p less than 0.05). The fall in blood pressure was attributable to a 12.1% increase in total peripheral conductance. Total norepinephrine spillover to plasma was reduced by 24% from a mean of 438.8 ng/min (p less than 0.05). Renal norepinephrine spillover fell by an average of 41% from 169.4 ng/min with bicycle training (p less than 0.05), accounting for the majority (66%) of the fall in total norepinephrine spillover. Renal vascular conductance was increased by 10% (p less than 0.05), but this constituted only 18% of the increase in total peripheral conductance. There was no change in cardiac norepinephrine spillover. The reduction in resting sympathetic activity with regular endurance exercise is largely confined to the kidney. The magnitude of the fall in renal vascular resistance, however, is insufficient to directly account for the blood pressure-lowering effect of exercise, although other effects of inhibition of the renal sympathetic outflow may be important.

Adult↗

Assessment of hemodynamic function and tolerance to ischemia in the absence or presence of calcium antagonists in hearts of isoproterenol-treated, exercise-trained, and sedentary rats.

The effects of cardiac hypertrophy on the structure, function and tolerance to ischemia of rat hearts have been investigated. Multiple injections of low doses of isoproterenol (ISO) resulted in an increase of heart weight/body weight ratio by 60%, and a decrease of myocardial creatine kinase activity by 25%, as compared to normal rats. Compared to age-matched control rats, rats submitted to a swimming program had a higher heart weight by 20%, but similar values of heart weight to body weight ratio. In isolated perfusion, the functional capacities of hearts from ISO-treated rats were severely depressed compared to normal rat hearts whereas exercise-trained rat hearts performed as well or even better than control hearts. The functional recovery of ISO-treated hearts following cardioplegia-induced arrest for 20 min at 37 degrees C was significantly worse than the recovery of normal hearts, but hearts of exercise-trained rats showed a significantly better recovery than control hearts. Exercise training results in improvement of myocardial blood supply resulting in better preservation of the heart during ischemia, compared to normal hearts. Addition of a combination of verapamil and diltiazem to the cardioplegic solution followed by ischemic arrest for 20 min at 37 degrees C resulted for ISO-treated rat hearts in an improved recovery of cardiac output (99%) compared to cardioplegia in the absence of these drugs (72%). In exercise-trained and control rat hearts, calcium antagonists improved the recovery from cardioplegic arrest of cardiac output from 90% to 92% and from 71% to 87%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Abdominal and hip flexor muscle activation during various training exercises.

The purpose of this study was to provide objective information on the involvement of different abdominal and hip flexor muscles during various types of common training exercises used in rehabilitation and sport. Six healthy male subjects performed altogether 38 different static and dynamic training exercises trunk and hip flexion sit-ups, with various combinations of leg position and support, and bi- and unilateral leg lifts. Myoelectric activity was recorded with surface electrodes from the rectus abdominis, obliquus externus, obliquus internus, rectus femoris, and sartorius muscles and with indwelling fine-wire electrodes from the iliacus muscle. The mean electromyogram amplitude, normalised to the highest observed value, was compared between static and dynamic exercises separately. The hip flexors were highly activated only in exercises involving hip flexion, either lifting the whole upper body or the legs. In contrast, the abdominal muscles showed marked activation both during trunk and hip flexion sit-ups. In hip flexion sit-ups, flexed and supported legs increased hip flexor activation, whereas such modifications did not generally alter the activation level of the abdominals. Bilateral, but not unilateral, leg lifts required activation of abdominal muscles. In trunk flexion sit-ups an increased activation of the abdominal muscles was observed with increased flexion angle, whereas the opposite was true for hip flexion sit-ups. Bilateral leg lifts resulted in higher activity levels than hip flexion sit-ups for the iliacus and sartorius muscles, while the opposite was true for rectus femoris muscles. These data could serve as a basis for improving the design and specificity of test and training exercises.

Abdominal Muscles↗

Effects of exercise training on hearing ability.

This study was designed to determine whether improvements in both cardiovascular fitness and hearing sensitivity occurred following 2 months of aerobic exercise training. Seventeen moderately-low fit (VO2 peak <32 ml/kg/min) young adults were evaluated for cardiovascular fitness and pure-tone and temporary threshold shifts (TTS) at 2, 3, and 4 kHz before and following 10 min of noise. Subjects exercised for 8 weeks by cycling on a bicycle ergometer at 70% of their peak oxygen consumption (VO2 peak). Average VO2 peak increased 34% (p < 0.05) above pre-exercise training levels. Both pure-tone hearing (2 and 3 kHz) and TTS improved following 2 months of exercise training at the evaluated frequencies (2, 3, and 4 kHz) (p < 0.05). Cardiovascular health as indicated by VO2 peak was associated with hearing sensitivity. Although the mechanisms have not been identified, these results support the existence of a cardiovascular health-hearing synergism.

Adult↗

Effect of exercise training on heart rate variability in patients with new-onset left ventricular dysfunction after myocardial infarction.

BACKGROUND: Cardiac rehabilitation with exercise training alters sympathovagal control of heart rate variability (HRV) toward parasympathetic dominance in patients after acute myocardial infarction (MI). However, its effects on HRV in patients after MI with new-onset left ventricular dysfunction are yet unknown. We aimed to investigate the effects of 8 weeks of supervised, high-intensity exercise training on time- and frequency-domain measures of HRV in this selected patient population. METHODS AND RESULTS: Twenty-five men with an acute MI and a low ejection fraction were randomly assigned to enter or not to enter a training program in a regional rehabilitation center. HRV was evaluated before and after 1 and 2 months of training and at 12 months. Maximal exercise testing with respiratory gas exchange was performed at baseline and after training. Resting heart rate decreased (P <. 01) and the percentage of R-R intervals differing >50 ms from the preceding one (pNN50) increased (P <.05) after training. The standard deviation of R-R intervals (SDRR) tended to increase, but frequency-domain indexes remained unchanged. There was a significant decrease in SDRR (P <.05) and high-frequency power (P <.01) at 12 months in untrained patients. Exercise time increased by 38% and maximal oxygen uptake increased by 29% in the training group (P <. 01). CONCLUSIONS: Despite beneficial effects on clinical variables, exercise training did not markedly alter HRV indexes. A significant decrease in SDRR and high-frequency power in the control group suggests an ongoing process of sympathovagal imbalance in favor of sympathetic dominance in untrained patients after MI with new-onset left ventricular dysfunction.

Aged↗

Effects of home-based exercise training on neurovascular control in patients with heart failure.

BACKGROUND: The effect of home-based exercise training on neurovascular control in heart failure patients is unknown. AIMS: To test the hypothesis that home-based training would maintain the reduction in muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) acquired after supervised training. METHODS AND RESULTS: Twenty-nine patients (54+/-1.9 years, EF<40%) were randomised into two groups: untrained control (n=12) and exercise trained (n=17). Both groups underwent assessment of Quality of Life (QoL), MSNA, and forearm blood flow. The exercise group underwent a 4-month supervised training program followed by 4 months of home-based training. After the initial 4 months of training, patients in the exercise group showed a significant increase in peak VO(2) and reduction in MSNA, compared to the untrained group, but this was not maintained during 4 months of home-based training. In contrast, the decrease in FVR (56+/-3 vs. 46+/-4 vs. 40+/-2 U, p=0.008) and the improvement in QOL that were achieved during supervised training were maintained during home-based training. CONCLUSIONS: Home-based training following supervised training is a safe strategy to maintain improvements in QoL and reduction in FVR in chronic heart failure patients, but is an inadequate strategy to maintain fitness as estimated by peak VO(2) or reduction in neurohumoral activation.

Adult↗

The effects of exercise training programs on psychosocial improvement in uncomplicated postmyocardial infarction patients.

To determine the effects of exercise training programs on psychosocial improvement in uncomplicated postmyocardial infarction patients, 210 male patients hospitalized for an acute myocardial infarction (MI) were randomized to three week symptom limited treadmill (TM) plus home exercise training, TM plus medically supervised gym training, TM without formal exercise program or control, where patients were seen only at six months post MI. Patients in this sample were at low risk for psychosocial disturbance (13% were moderate to severely depressed, 23% reported marital disturbance and 3% were extremely anxious). Patients in the training groups improved from 3 to 26 weeks post MI on all depression and anxiety measures. The gym training group showed a significant reduction on one depression measure compared to no training and on one anxiety measure compared to controls.

Adaptation, Psychological↗

Effect of high- versus low-frequency exercise training in multidisciplinary cardiac rehabilitation on health-related quality of life.

BACKGROUND: The authors examined the importance of the frequency of aerobic exercise training in multidisciplinary rehabilitation in improving health-related quality of life in the short run in patients with documented coronary artery disease. METHODS: Patients (114 males and 16 females; age range, 32-70 years) were randomized into either a high-frequency or a low-frequency exercise training program (10 versus 2 sessions per week, respectively) as part of a 6-week multidisciplinary cardiac rehabilitation program. The General Health Questionnaire and the RAND-36 were used to assess changes in psychological distress and subjective health status. RESULTS: After 6 weeks, high-frequency patients reported significantly more positive, change in "psychological distress" (P < 0.05), "mental health" (P = 0.05), and "health change" (P < 0.01), than low-frequency patients. Apart from changes in mean scores, individual effect sizes indicated that a significantly greater percentage of high-frequency patients experienced substantial improvements in "psychological distress" (P < 0.01), "physical functioning" (P < 0.05), and "health change" (P < 0.05), compared with low-frequency patients. In addition, deterioration of quality of life was observed in a considerable number of high-frequency patients (ranging from 1.7% to 25.8% on the various measures). CONCLUSIONS: The frequency of aerobic exercise has a positive, independent effect on psychological outcomes after cardiac rehabilitation. However, this benefit after high-frequency rehabilitation appears to be limited to a subgroup of patients. Further investigation is required to identify these patients. Results provide input into recent controversies regarding the role of exercise training in cardiac rehabilitation.

Adult↗

Exercise training and myocardial remodeling in patients with reduced ventricular function: one-year follow-up with magnetic resonance imaging.

BACKGROUND: Exercise training is now an accepted therapeutic intervention in patients with reduced ventricular function after a myocardial infarction. However, there are conflicting reports on the effects of training on the remodeling process of the heart, and previous studies have only assessed short-term effects of training. METHODS AND RESULTS: Twenty-five patients with reduced ventricular function after myocardial infarction were randomly assigned to an intensive 2-month exercise training program or to a control group (control group: n = 13, aged 55 +/- 7 years, ejection fraction 33.3% +/- 6%; exercise group: n = 12, aged 56 +/- 5 years, ejection fraction 31.5% +/- 7%) and followed up for 1 year. Measures of left ventricular size, function, and wall thickness in the infarct and noninfarct areas were made by magnetic resonance imaging at baseline, after the 2-month training period, and 1 year later. Maximal oxygen uptake increased in the trained group, from 19.7 +/- 3 mL/kg per minute at baseline to 25.1 +/- 5 and 24.2 +/- 5 mL/kg per minute after 2 months and 1 year, respectively (P <.05 vs baseline for both), whereas the control group did not change significantly. Ejection fraction, end-diastolic volumes, and end-systolic volumes did not change at any measurement point throughout the study period in either the trained or control groups. Myocardial wall thickness measurements at end-diastole and end-systole and their differences determined by magnetic resonance imaging yielded no significant interactions between groups. When myocardial wall thickness measurements were classified by infarct or noninfarct areas, no differences were observed between groups over the study period. CONCLUSIONS: Intensive exercise training in patients with reduced ventricular function resulted in a significant improvement in exercise capacity after 2 months, and this improvement was sustained over 1 year. In contrast to some recent reports, training had no deleterious effects on left ventricular volume, function, or wall thickness regardless of infarct area.

Exercise Test↗

Vascular transport capacity of hindlimb muscles of exercise-trained rats.

The purpose of this study was to determine whether chronic exercise training is associated with increased vascular flow capacity and capillary exchange capacity in skeletal muscles. One group of male Sprague-Dawley rats was cage confined for a period of 13-17 wk (sedentary control, C) and a second was trained for 1 h/day at a speed of 30 m/min up a 5 degrees incline for 13-17 wk (exercise trained, ET). Studies were conducted with maximally dilated (papaverine) isolated hindquarters of 13 C rats and 10 ET rats perfused with Tyrode's solution containing 5% albumin. Vascular flow capacity was estimated by measuring total and regional flows at three to five different perfusion pressures. Capillary exchange capacity was estimated by measuring maximal capillary filtration coefficients and capillary diffusion capacity for 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA). The efficacy of the training was shown by significant increases in succinate dehydrogenase activities of the vastus intermedius muscle. Total hindquarter flow capacity was 50% higher in the ET rats. Regional flow data indicated that the higher total flow was due to increased muscle flow (85%), with the high-oxidative muscle tissue having the greatest increases (e.g., 200% increase in red gastrocnemius muscle). The maximal capillary diffusion capacity values for the ET rats were 70% greater than control values. However, the capillary filtration capacity values of the C and ET rats were not different. We conclude that the vascular transport capacity of the high-oxidative areas of extensor muscles is increased by endurance training.

Animals↗

Effects of high intensity exercise training on cardiovascular function, oxygen uptake, internal oxygen transport and osmotic balance in chinook salmon (Oncorhynchus tshawytscha) during critical speed swimming.

To examine cardiorespiratory plasticity, cardiovascular function, oxygen consumption, oxygen delivery and osmotic balance were measured at velocities up to critical swimming speed (Ucrit) in seawater-adapted chinook salmon. We used two groups of fish. The control group had swum continuously for 4 months at a low intensity (0.5 BLs(-1)) and the other was given a high-intensity training regimen (a Ucrit swim test on alternate days) over the same period of time. Compared with available data for other salmonid species, the control group had a higher maximum oxygen consumption (MO2max; 244 micromol O2 min(-1) kg(-1)), cardiac output (Qmax; 65 ml min(-1) kg(-1)) and blood oxygen content (CaO2; 15 ml O2 dl(-1)). Exercise training caused a 50% increase in MO2max without changing either Ucrit or CaO2, even though there were small but significant increases in hematocrit, hemoglobin concentration and relative ventricular mass. During swimming, however, exercise-trained fish experienced a smaller decrease in body mass and muscle moisture, a smaller increase in plasma osmolality, and reduced venous oxygen stores compared with control fish. Consequently, exercise training apparently diminished the osmo-respiratory compromise, but improved oxygen extraction at the tissues. We conclude that the training-induced increase in MO2max provided benefits to systems other than the locomotory system, such as osmoregulation, enabling trained fish to better multitask physiological functions while swimming. Furthermore, because a good interspecific correlation exists between MO2max and arterial oxygen supply (TO2max; r2=0.99) among temperate fish species, it is likely that CaO2 and Qmax are principal loci for cardiorespiratory evolutionary adaptation but not for intraspecific cardiorepiratory plasticity as revealed by high intensity exercise training.

Animals↗

Effect of controlled exercise training in coronary artery disease patients with and without left ventricular dysfunction assessed by cardiopulmonary indices.

Cardiopulmonary indices were used to evaluate the effect of controlled exercise training prescribed on the basis of the heart rate at the ventilatory anaerobic threshold in coronary artery disease patients with and without impaired left ventricular function. Fifty-two patients aged 38-75 years were divided into four groups. The first three groups included patients with a left ventricular ejection fraction of > 45% at rest, as follows: group 1, 10 patients with single-vessel disease; group 2, 12 patients with two-vessel disease; group 3, 10 patients with three-vessel disease. Group 4 comprised 20 patients with left ventricular dysfunction (ejection fraction < 35%). The left ventricular ejection fraction was assessed by multigated acquisition radionuclear study. All patients underwent a cardiopulmonary exercise test before and after the program which lasted 6-9 months. The variables measured were oxygen consumption (VO2), CO2 output, minute ventilation, O2 pulse, and ventilatory anaerobic threshold. Significant improvements in maximal VO2, maximal O2 pulse, and ventilatory anaerobic threshold level were observed in groups 1, 2, and 4 (p < 0.1-0.0001), but not in group 3. These findings indicate that the overall cardiac function, as evaluated by cardiopulmonary indices, improves in patients with one- or two-vessel disease with good left ventricular function and in patients with impaired left ventricular function following an exercise training program. Severe coronary disease seems to limit improvement, even in the presence of a good left ventricular function. The results validate the heart rate at the ventilatory anaerobic threshold as the optimal training heart rate in coronary artery disease patients and the cardiopulmonary exercise test as a sensitive tool for evaluating exercise training results.

Adult↗

Effect of exercise training and chronic ethanol ingestion on cholinesterase activity and lipid peroxidation in blood and brain regions of rat.

1. This study examines the effects of exercise training and chronic ethanol consumption on cholinesterase activity and its relationship to lipid peroxidation in blood and brain regions of rat. 2. Exercise training (6.5 weeks) decreased acetylcholinesterase (AChE) activity significantly (64% of control) in hypothalamus and increased AChE activity in cerebral cortex (149% of control), whereas, malondialdehyde (MDA) levels increased in hypothalamus (129% of control) and decreased in cortex, striatum, and cerebellum (50%, 69% and 75% of control), respectively. 3. Chronic ethanol ingestion (2.0 gm/kg, p.o. for 6.5 weeks) significantly increased butyrylcholinesterase (BuChE) activity in plasma (136% of control) and decreased AChE activity in hypothalamus (63% of control), whereas, MDA levels increased in hypothalamus, cortex, and plasma (140%, 130% and 220% of control), respectively. 4. The combination significantly increased BuChE activity (173% of control) in plasma and decreased AChE activity (71% of control) in hypothalamus and (57% of control) in cerebellum, whereas, MDA levels increased in hypothalamus, cerebellum, medulla and plasma (134%, 128%, 140% and 309% of control), respectively. 5. Exercise training, chronic ethanol ingestion, and combination selectively inhibited hypothalamic AChE and the inhibition was correlated with increased lipid peroxidation (r = 0.11, 0.41 and 0.45) which may perturb hypothalamic function. The combination enhanced the peripheral stress response by increasing plasma BuChE activity and lipid peroxidation.

Animals↗

Beneficial effects on blood pressure and lipid profile of programmed exercise training in subjects with white coat hypertension.

BACKGROUND: Patients with white coat hypertension comprise a substantial portion of the hypertensive population. Previous reports have shown that moderate-intensity regular exercise training in patients with mild hypertension usually reduces blood pressure (BP), but there is a lack of data regarding individuals with white coat hypertension. This study was performed to evaluate whether programmed exercise was effective in reducing BP in patients with white coat hypertension and whether it also had beneficial effects on other biochemical parameters. METHODS: A total of 42 patients (23 men and 19 women) with white coat hypertension (mean 24-h ambulatory BP 119.2 +/- 6.6/78.3 +/- 5.8 mm Hg) were divided randomly into two groups: control (n = 20) (no exercise), and moderate-intensity exercise (n = 22). The training group exercised three times per week at the prescribed exercise intensity using a treadmill exercise program. Blood pressure, heart rate, and biochemical parameters were monitored every 4 weeks for 12 weeks. RESULTS: Significant reductions in clinic and ambulatory BPs were seen in the exercise group after only 4 weeks regular exercise training and these persisted over the 12-week study. The mean maximal reductions in clinic BP were 11 mm Hg for systolic and 5 mm Hg for diastolic pressure. Significant reductions were found in plasma total cholesterol (-6.1%), low-density lipoprotein cholesterol (LDL-C) (-14.1%), and triglyceride (-11.4%). Elevation of high-density lipoprotein cholesterol (HDL-C) (+11.2%) was also noted. CONCLUSIONS: These data, which are clinically significant, suggest that 12 weeks of exercise training can result in successful reduction of BP and favorable changes in the lipid profile that would be beneficial to patients with white coat hypertension.

Adult↗

Effect of exercise training on plasma catecholamines and haemodynamics of adolescent hypertensives during rest, submaximal exercise and orthostatic stress.

Twelve adolescents with essential hypertension were studied to determine the effect of exercise training on plasma catecholamine concentrations, blood pressure and cardiovascular haemodynamics at rest and during submaximal exercise and orthostatic stress. Maximal oxygen consumption (VO2max) increased 13% with training while body weight and body fat did not change. Resting systolic and diastolic blood pressures decreased significantly with training, while plasma norepinephrine and epinephrine levels were unchanged. The increase in systolic blood pressure in response to standing was significantly lower after training, while the plasma catecholamine response was not significantly different. At the same absolute work rate after training, the subjects' systolic and diastolic blood pressures, heart rates, and plasma norepinephrine and epinephrine levels were significantly lower than before training. At the same relative work rate after training, the blood pressure response was the same as before training despite significantly higher plasma norepinephrine levels. Thus, the training-induced changes in resting blood pressures and blood pressure responses to orthostatic and submaximal exercise stress cannot be attributed to decreases in plasma catecholamine levels.

Adaptation, Physiological↗

[Development and evaluation of a new target heart rate formula for the adequate exercise training level in healthy subjects].

Little data is available recommending the adequate exercise level for physical fitness, so we hypothesized that the anaerobic threshold (AT) point is an ideal exercise level. We aimed to determine a new target heart rate formula for the adequate exercise training level in healthy subjects. This study first developed a new formula in 405 subjects (221 males, 184 females, mean age 48.9 +/- 12.3 years). The AT was determined during cycle ergometer exercise with continuous respiratory gas measurements. The correlation of heart rate at the AT to resting heart rate, age and gender was analyzed by the multiple regression method. Based on this correlation, a new formula calculating target heart rate was established as 74.8 + 0.76 x (resting heart rate) - 0.27 x (age) + 7.3 x S (male: 0 or female: 1). This formula was then compared to Blackburn's method in 210 subjects (139 males, 71 females, mean age 44.5 +/- 14.4 years). The difference between the new target heart rate and the heart rate at the AT was significantly lower than that between the target heart rate by Blackburn's method [(220 - age) x 0.7] and the heart rate at the AT (8.8 +/- 6.3 vs 12.7 +/- 8.2 beat/min, p < 0.001). The resting heart rate and gender are important factors in determining the target heart rate for exercise. This new formula indicates the adequate exercise training level more accurately in healthy subjects.

Adult↗

Exercise training for African Americans with disabilities residing in difficult social environments.

OBJECTIVE: To examine the feasibility, efficacy, and safety of a structured 12-week exercise training program for a predominantly African-American group of adults with multiple health conditions who reside in difficult social environments. METHODS: A total of 37 females and 7 males (mean age, 54.1 years) participated in an exercise training regimen 3 days per week for 60 minutes per day (cardiovascular, 30 minutes; strength, 20 minutes; and flexibility, 10 minutes). Outcome measures included peak VO(2) (mL min(-1), mL kg(-1) min(-1)); upper and lower body strength (strength); hand-grip strength (GS); body weight (BW); total skin folds (TS); waist-to-hip ratio (WHR); hamstring/low-back flexibility (HLBF); and shoulder flexibility (SF). RESULTS: Compared to the control group, the exercise group showed significant gains in peak VO(2) (p < 0.01); strength (p < 0.01); and body composition (TS, p < 0.01). There was no significant difference between the exercise and control groups on BW, WHR, HLBF, and GS. Of a total 1116 exercise sessions (31 experimental participants x 36 sessions), 87% of the sessions were attended. CONCLUSIONS: A structured exercise-training program can provide substantial improvement in strength and cardiovascular fitness in low-income, sedentary adults with multiple chronic conditions and/or risk factors for chronic conditions. Future research should explore simple home-based and community-based physical activity interventions that provide ongoing support for increasing and maintaining physical activity participation in this cohort.

Black or African American↗

Enhanced neuronal nitric oxide synthase expression is central to cardiac vagal phenotype in exercise-trained mice.

We investigated whether enhanced cardiac vagal responsiveness elicited by exercise training is dependent on neuronal nitric oxide synthase (NOS-1), since the NO-cGMP pathway facilitates acetylcholine release. Isolated atria with intact right vagal innervation were taken from male mice (18-22 weeks old) after a period of 10 weeks voluntary wheel-running (+EX, n = 27; peaked 9.8 +/- 0.6 km day(-1) at 5 weeks), and from mice housed in cages without wheels (-EX, n = 27). Immunostaining of whole atria for NOS-1 identified intrinsic neurones, all of which co-localized with choline acetyltransferase-positive ganglia. Western blot analysis confirmed that NOS-1 protein level was significantly greater in +EX compared to -EX atria (P < 0.05, unpaired t test). Basal heart rates (HR) were slower in +EX than in -EX atria (322 +/- 6 versus 360 +/- 7 beats min(-1); P < 0.05, unpaired t test) However, in +EX atria, HR responses to vagal stimulation (VNS, 3 and 5 Hz) were significantly enhanced compared to -EX atria (3 Hz, +EX: -76 +/- 8 beats min(-1) versus -EX: -62 +/- 7 beats min(-1); 5 Hz, +EX: -106 +/- 4 beats min(-1) versus -EX: -93 +/- 3 beats min(-1); P < 0.01, unpaired t test). Inhibition of NOS-1 with vinyl-L-N-5-(1-imino-3-butenyl)-L-ornithine (L-VNIO, 100 microM) or soluble guanylyl cyclase with 1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ, 10 microM) abolished the difference in HR responses to VNS between +EX and -EX atria, and effects of L-VNIO were reversed by excess L-arginine (1 mM; P < 0.01, ANOVA). There were no differences between the HR responses to the bath-applied acetylcholine analogue carbamylcholine chloride in +EX and -EX atria (IC(50) concentrations were 5.9 +/- 0.4 microM (-EX) and 5.7 +/- 0.4 microM (+EX)), suggesting that the changes in vagal responsiveness resulted from presynaptic facilitation of neurotransmission. In conclusion, NOS-1 appears to be a key protein in generating the cardiac vagal gain of function elicited by exercise training.

Animals↗