Impact of combined NO and PG blockade on rapid vasodilation in a forearm mild-to-moderate exercise transition in humans

We tested the hypothesis that nitric oxide (NO) and prostaglandins (PGs) contribute to the rapid vasodilation that accompanies a transition from mild to moderate exercise. Nine healthy volunteers (2 women and 7 men) lay supine with forearm at heart level. Subjects were instrumented for continuous brachial artery infusion of saline (control condition) or combined infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) and ketorolac (drug condition) to inhibit NO synthase and cyclooxygenase, respectively. A step increase from 5 min of steady-state mild (5.4 kg) rhythmic, dynamic forearm handgrip exercise (1 s of contraction followed by 2 s of relaxation) to moderate (10.9 kg) exercise for 30 s was performed. Steady-state forearm blood flow (FBF; Doppler ultrasound) and forearm vascular conductance (FVC) were attenuated in drug compared with saline (control) treatment: FBF = 196.8 +/- 30.8 vs. 281.4 +/- 34.3 ml/min and FVC = 179.3 +/- 29.4 vs. 277.8 +/- 34.8 ml.min(-1).100 mmHg(-1) (both P < 0.01). FBF and FVC increased from steady state after release of the initial contraction at the higher workload in saline and drug conditions: DeltaFBF = 72.4 +/- 8.7 and 52.9 +/- 7.8 ml/min, respectively, and DeltaFVC = 66.3 +/- 7.3 and 44.1 +/- 7.0 ml.min(-1).100 mmHg(-1), respectively (all P < 0.05). The percent DeltaFBF and DeltaFVC were not different during saline infusion or combined inhibition of NO and PGs: DeltaFBF = 27.2 +/- 3.1 and 28.1 +/- 3.8%, respectively (P = 0.78) and DeltaFVC = 25.7 +/- 3.2 and 26.0 +/- 4.0%, respectively (P = 0.94). The data suggest that NO and vasodilatory PGs are not obligatory for rapid vasodilation at the onset of a step increase from mild- to moderate-intensity forearm exercise. Additional vasodilatory mechanisms not dependent on NO and PG release contribute to the immediate and early increase in blood flow in an exercise-to-exercise transition.     

Low-dose estrogen therapy does not change postexercise hypotension, sympathetic nerve activity reduction, and vasodilation in healthy postmenopausal women

The aim of this study was to determine whether estrogen therapy enhances postexercise muscle sympathetic nerve activity (MSNA) decrease and vasodilation, resulting in a greater postexercise hypotension. Eighteen postmenopausal women received oral estrogen therapy (ET; n=9, 1 mg/day) or placebo (n=9) for 6 mo. They then participated in one 45-min exercise session (cycle ergometer at 50% of oxygen uptake peak) and one 45-min control session (seated rest) in random order. Blood pressure (BP, oscillometry), heart rate (HR), MSNA (microneurography), forearm blood flow (FBF, plethysmography), and forearm vascular resistance (FVR) were measured 60 min later. FVR was calculated. Data were analyzed using a two-way ANOVA. Although postexercise physiological responses were unaltered, HR was significantly lower in the ET group than in the placebo group (59+/-2 vs. 71+/-2 beats/min, P<0.01). In both groups, exercise produced significant decreases in systolic BP (145+/-3 vs. 154+/-3 mmHg, P=0.01), diastolic BP (71+/-3 vs. 75+/-2 mmHg, P=0.04), mean BP (89+/-2 vs. 93+/-2 mmHg, P=0.02), MSNA (29+/-2 vs. 35+/-1 bursts/min, P<0.01), and FVR (33+/-4 vs. 55+/-10 units, P=0.01), whereas it increased FBF (2.7+/-0.4 vs. 1.6+/-0.2 ml x min(-1) x 100 ml(-1), P=0.02) and did not change HR (64+/-2 vs. 65+/-2 beats/min, P=0.3). Although ET did not change postexercise BP, HR, MSNA, FBF, or FVR responses, it reduced absolute HR values at baseline and after exercise.     

Systemic hypoxia and vasoconstrictor responsiveness in exercising human muscle.

Exercise blunts sympathetic alpha-adrenergic vasoconstriction (functional sympatholysis). We hypothesized that sympatholysis would be augmented during hypoxic exercise compared with exercise alone. Fourteen subjects were monitored with ECG and pulse oximetry. Brachial artery and antecubital vein catheters were placed in the nondominant (exercising) arm. Subjects breathed hypoxic gas to titrate arterial O2 saturation to 80% while remaining normocapnic via a rebreath system. Baseline and two 8-min bouts of rhythmic forearm exercise (10 and 20% of maximum) were performed during normoxia and hypoxia. Forearm blood flow, blood pressure, heart rate, minute ventilation, and end-tidal CO2 were measured at rest and during exercise. Vasoconstrictor responsiveness was determined by responses to intra-arterial tyramine during the final 3 min of rest and each exercise bout. Heart rate was higher during hypoxia (P < 0.01), whereas blood pressure was similar (P = 0.84). Hypoxic exercise potentiated minute ventilation compared with normoxic exercise (P < 0.01). Forearm blood flow was higher during hypoxia compared with normoxia at rest (85 +/- 9 vs. 66 +/- 7 ml/min), at 10% exercise (276 +/- 33 vs. 217 +/- 27 ml/min), and at 20% exercise (464 +/- 32 vs. 386 +/- 28 ml/min; P < 0.01). Arterial epinephrine was higher during hypoxia (P < 0.01); however, venoarterial norepinephrine difference was similar between hypoxia and normoxia before (P = 0.47) and during tyramine administration (P = 0.14). Vasoconstriction to tyramine (%decrease from pretyramine values) was blunted in a dose-dependent manner with increasing exercise intensity (P < 0.01). Interestingly, vasoconstrictor responsiveness tended to be greater (P = 0.06) at rest (-37 +/- 6% vs. -33 +/- 6%), at 10% exercise (-27 +/- 5 vs. -22 +/- 4%), and at 20% exercise (-22 +/- 5 vs. -14 +/- 4%) between hypoxia and normoxia, respectively. Thus sympatholysis is not augmented by moderate hypoxia nor does it contribute to the increased blood flow during hypoxic exercise.     

Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset of exercise.

The purpose of this study was to test the hypothesis that sympathetic vasoconstriction is rapidly blunted at the onset of forearm exercise. Nine healthy subjects performed 5 min of moderate dynamic forearm handgrip exercise during -60 mmHg lower body negative pressure (LBNP) vs. without (control). Beat-by-beat forearm blood flow (Doppler ultrasound), arterial blood pressure (finger photoplethysmograph), and heart rate were collected. LBNP elevated resting heart rate by approximately 45%. Mean arterial blood pressure was not significantly changed (P = 0.196), but diastolic blood pressure was elevated by approximately 10% and pulse pressure was reduced by approximately 20%. At rest, there was a 30% reduction in forearm vascular conductance (FVC) during LBNP (P = 0.004). The initial rapid increase in FVC with exercise onset reached a plateau between 10 and 20 s of 126.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in control vs. only 101.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in LBNP (main effect of condition, P = 0.003). This difference was quickly abolished during the second, slower phase of adaptation in forearm vascular tone to steady state. These data are consistent with a rapid onset of functional sympatholysis, in which local substances released with the onset of muscle contractions impair sympathetic neural vasoconstrictor effectiveness.     

Metabolic forearm vasodilation is enhanced following Bier block with phentolamine

The extent to which sympathetic nerve activity restrains metabolic vasodilation in skeletal muscle remains unclear. We determined forearm blood flow (FBF; ultrasound/Doppler) and vascular conductance (FVC) responses to 10 min of ischemia [reactive hyperemic blood flow (RHBF)] and 10 min of systemic hypoxia (inspired O(2) fraction = 0.1) before and after regional sympathetic blockade with the alpha-receptor antagonist phentolamine via Bier block in healthy humans. In a control group, we performed sham Bier block with saline. Consistent with alpha- receptor inhibition, post-phentolamine, basal FVC (FBF/mean arterial pressure) increased (pre vs. post: 0.42 +/- 0.05 vs. 1.03 +/- 0.21 units; P < 0.01; n = 12) but did not change in the saline controls (pre vs. post: 0.56 +/- 0.14 vs. 0.53 +/- 0.08 units; P = not significant; n = 5). Post-phentolamine, total RHBF (over 3 min) increased substantially (pre vs. post: 628 +/- 75 vs. 826 +/- 92 ml/min; P < 0.01) but did not change in the controls (pre vs. post: 618 +/- 66 vs. 661 +/- 35 ml/min; P = not significant). In all conditions, compared with peak RHBF, peak skin reactive hyperemia was markedly delayed. Furthermore, post-phentolamine (pre vs. post: 0.43 +/- 0.06 vs. 1.16 +/- 0.17 units; P < 0.01; n = 8) but not post-saline (pre vs. post: 0.93 +/- 0.16 vs. 0.87 +/- 0.19 ml/min; P = not significant; n = 5), the FVC response to hypoxia (arterial O(2) saturation = 77 +/- 1%) was markedly enhanced. These data suggest that sympathetic vasoconstrictor nerve activity markedly restrains skeletal muscle vasodilation induced by local (forearm ischemia) and systemic (hypoxia) vasodilator stimuli.     

Blood flow conditions in the proximal pulmonary arteries and vena cavae: healthy children during upright cycling exercise

Diagnostic testing in patients with congenital heart disease is usually performed supine and at rest, conditions not representative of their typical hemodynamics. Upright exercise measurements of blood flow may prove valuable in the assessment of these patients, but data in normal subjects are first required. With the use of a 0.5-T open magnet, a magnetic resonance-compatible exercise cycle, and cine phase-contrast techniques, time-dependent blood flow velocities were measured in the right (RPA), left (LPA), and main (MPA) pulmonary arteries and superior (SVC) and inferior (IVC) vena cavae of 10 healthy 10- to 14-yr-old subjects. Measurements were made at seated rest and during upright cycling exercise (150% resting heart rate). Mean blood flow (l/min) and reverse flow index were computed from the velocity data. With exercise, RPA and LPA mean flow increased 2.0 +/- 0.5 to 3.7 +/- 0.7 (P < 0.05) and 1.6 +/- 0.4 to 2.9 +/- 0.8 (P < 0.05), respectively. Pulmonary reverse flow index (rest vs. exercise) decreased with exercise as follows: MPA: 0.014 +/- 0.012 vs. 0.006 +/- 0.006 [P = not significant (NS)], RPA: 0.005 +/- 0.004 vs. 0.000 +/- 0.000 (P < 0.05), and LPA: 0.041 +/- 0.019 vs. 0.014 +/- 0.016 (P < 0.05). SVC and IVC flow increased from 1.5 +/- 0.2 to 1.9 +/- 0.6 (P = NS) and 1.6 +/- 0.4 to 4.9 +/- 1.3 (P < 0.05), respectively. A 56/44% RPA/LPA flow distribution at both rest and during exercise suggests blood flow distribution is dominated by distal pulmonary resistance. Reverse flow in the MPA appears to originate solely from the LPA while the RPA is in relative isolation. During seated rest, the SVC-to-IVC venous return ratio is 50/50%. With light/moderate cycling exercise, IVC flow increases by threefold, whereas SVC remains essentially constant.     

Evidence for a rapid vasodilatory contribution to immediate hyperemia in rest-to-mild and mild-to-moderate forearm exercise transitions in humans.

Controversy exists regarding the contribution of a rapid vasodilatory mechanism(s) to immediate exercise hyperemia. Previous in vivo investigations have exclusively examined rest-to-exercise (R-E) transitions where both the muscle pump and early vasodilator mechanisms may be activated. To isolate vasodilatory onset, the present study investigated the onset of exercise hyperemia in an exercise-to-exercise (E-E) transition, where no further increase in muscle pump contribution would occur. Eleven subjects lay supine and performed a step increase from rest to 3 min of mild (10% maximal voluntary contraction), rhythmic, dynamic forearm handgrip exercise, followed by a further step to moderate exercise (20% maximal voluntary contraction) in each of arm above (condition A) or below (condition B) heart level. Beat-by-beat measures of brachial arterial blood flow (Doppler ultrasound) and blood pressure (arterial tonometry) were performed. We observed an immediate increase in forearm vascular conductance in E-E transitions, and the magnitude of this increase matched that of the R-E transitions within each of the arm positions (condition A: E-E, 52.8 +/- 10.7 vs. R-E, 60.3 +/- 11.7 ml.min(-1).100 mmHg(-1), P = 0.66; condition B: E-E, 43.2 +/- 12.8 vs. R-E, 33.9 +/- 8.2 ml.min(-1).100 mmHg(-1), P = 0.52). Furthermore, changes in forearm vascular conductance were identical between R-E and E-E transitions over the first nine contraction-relaxation cycles in condition A. The immediate and identical increase in forearm vascular conductance in R-E and E-E transitions within arm positions provides strong evidence that rapid vasodilation contributes to immediate exercise hyperemia in humans. Specific vasodilatory mechanisms responsible remain to be determined.     

Cutaneous blood flow during exercise is higher in endurance-trained humans.

This study determined whether cutaneous blood flow during exercise is different in endurance-trained (Tr) compared with untrained (Untr) subjects. Ten Tr and ten Untr men (62.4 +/- 1.7 and 44.2 +/- 1.8 ml. kg(-1). min(-1), respectively; P < 0.05) underwent three 20-min cycling-exercise bouts at 50, 70, and 90% peak oxygen uptake in this order, with 30 min rest in between. The environmental conditions were neutral ( approximately 23-24 degrees C, 50% relative humidity, front and back fans at 2.5 m/s). Because of technical difficulties, only seven Tr and seven Untr subjects completed all forearm blood flow and laser-Doppler cutaneous blood flow (CBF) measurements. Albeit similar at rest, at the end of all three exercise bouts, forearm blood flow was approximately 40% higher in Tr compared with Untr subjects (50%: 4.64 +/- 0.50 vs. 3. 17 +/- 0.20, 70%: 6.17 +/- 0.61 vs. 4.41 +/- 0.37, 90%: 6.77 +/- 0. 62 vs. 5.01 +/- 0.37 ml. 100 ml(-1). min(-1), respectively; n = 7; all P < 0.05). CBF was also higher in Tr compared with Untr subjects at all relative intensities (n = 7; all P < 0.05). However, esophageal temperature was not different in Tr compared with Untr subjects at the end of any of the aforementioned exercise bouts (50%: 37.8 +/- 0.1 vs. 37.9 +/- 0.1 degrees C, 70%: 38.1 +/- 0.1 vs. 38.1 +/- 0.1 degrees C, and 90%: 38.8 +/- 0.1 vs. 38.6 +/- 0.1 degrees C, respectively). We conclude that a higher CBF may allow Tr subjects to achieve an esophageal temperature similar to that of Untr, despite their higher metabolic rates and thus higher heat production rates, during exercise at 50-90% peak oxygen uptake.     

Forearm blood flow follows work rate during submaximal dynamic forearm exercise independent of sex.

To test the hypothesis that sex influences forearm blood flow (FBF) during exercise, 15 women and 16 men of similar age [women 24.3 +/- 4.0 (SD) vs. men 24.9 +/- 4.5 yr] but different forearm muscle strength (women 290.7 +/- 44.4 vs. men 509.6 +/- 97.8 N; P < 0.05) performed dynamic handgrip exercise as the same absolute workload was increased in a ramp function (0.25 W/min). Task failure was defined as the inability to maintain contraction rate. Blood pressure and FBF were measured on separate arms during exercise by auscultation and Doppler ultrasound, respectively. Muscle strength was positively correlated with endurance time (r = 0.72, P < 0.01) such that women had a shorter time to task failure than men (450.5 +/- 113.0 vs. 831.3 +/- 272.9 s; P < 0.05). However, the percentage of maximal handgrip strength achieved at task failure was similar between sexes (14% maximum voluntary contraction). FBF was similar between women and men throughout exercise and at task failure (women 13.6 +/- 5.3 vs. men 14.5 +/- 4.9 ml.min(-1).100 ml(-1)). Mean arterial pressure was lower in women at rest and during exercise; thus calculated forearm vascular conductance (FVC) was higher in women during exercise but similar between sexes at task failure (women 0.13 +/- 0.05 vs. men 0.11 +/- 0.04 ml.min(-1).100 ml(-1).mmHg(-1)). In conclusion, the similar FBF during exercise was achieved by a higher FVC in the presence of a lower MAP in women than men. Still, FBF remained coupled to work rate (and presumably metabolic demand) during exercise irrespective of sex.     

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.     

Effect of short-term sprint interval training on human skeletal muscle carbohydrate metabolism during exercise and time-trial performance.

Our laboratory recently showed that six sessions of sprint interval training (SIT) over 2 wk increased muscle oxidative potential and cycle endurance capacity (Burgomaster KA, Hughes SC, Heigenhauser GJF, Bradwell SN, and Gibala MJ. J Appl Physiol 98: 1895-1900, 2005). The present study tested the hypothesis that short-term SIT would reduce skeletal muscle glycogenolysis and lactate accumulation during exercise and increase the capacity for pyruvate oxidation via pyruvate dehydrogenase (PDH). Eight men [peak oxygen uptake (VO2 peak)=3.8+/-0.2 l/min] performed six sessions of SIT (4-7x30-s "all-out" cycling with 4 min of recovery) over 2 wk. Before and after SIT, biopsies (vastus lateralis) were obtained at rest and after each stage of a two-stage cycling test that consisted of 10 min at approximately 60% followed by 10 min at approximately 90% of VO2 peak. Subjects also performed a 250-kJ time trial (TT) before and after SIT to assess changes in cycling performance. SIT increased muscle glycogen content by approximately 50% (main effect, P=0.04) and the maximal activity of citrate synthase (posttraining: 7.8+/-0.4 vs. pretraining: 7.0+/-0.4 mol.kg protein -1.h-1; P=0.04), but the maximal activity of 3-hydroxyacyl-CoA dehydrogenase was unchanged (posttraining: 5.1+/-0.7 vs. pretraining: 4.9+/-0.6 mol.kg protein -1.h-1; P=0.76). The active form of PDH was higher after training (main effect, P=0.04), and net muscle glycogenolysis (posttraining: 100+/-16 vs. pretraining: 139+/-11 mmol/kg dry wt; P=0.03) and lactate accumulation (posttraining: 55+/-2 vs. pretraining: 63+/-1 mmol/kg dry wt; P=0.03) during exercise were reduced. TT performance improved by 9.6% after training (posttraining: 15.5+/-0.5 vs. pretraining: 17.2+/-1.0 min; P=0.006), and a control group (n=8, VO2 peak=3.9+/-0.2 l/min) showed no change in performance when tested 2 wk apart without SIT (posttraining: 18.8+/-1.2 vs. pretraining: 18.9+/-1.2 min; P=0.74). We conclude that short-term SIT improved cycling TT performance and resulted in a closer matching of glycogenolytic flux and pyruvate oxidation during submaximal exercise.     

Effect of positive-pressure breathing on cardiovascular and thermoregulatory responses to exercise

Five healthy male volunteers performed 20 min of both seated and supine cycle-ergometer exercise (intensity, 50% maximal O2 uptake) in a warm environment (Tdb = 30 degrees C, relative humidity = 40-50%) with and without breathing 10 cmH2O of continuous positive airway pressure (CPAP). The final esophageal temperature (Tes) at the end of 20 min of seated exercise was significantly higher during CPAP (mean difference = 0.18 +/- 0.04 degree C, P less than 0.05) compared with control breathing (C). The Tes threshold for forearm vasodilation was significantly higher (P less than 0.05) during seated CPAP exercise than C (C = 37.16 +/- 0.13 degrees C, CPAP = 37.38 + 0.12 degree C). The highest forearm blood flow (FBF) at the end of exercise was significantly lower (P less than 0.05) during seated exercise with CPAP (mean +/- SE % difference from C = -30.8 +/- 5.8%). During supine exercise, there were no significant differences in the Tes threshold, highest FBF, or final Tes with CPAP compared with C. The added strain on the cardiovascular system produced by CPAP during seated exercise in the heat interacts with body thermoregulation as evidenced by elevated vasodilation thresholds, reduced peak FBF, and slightly higher final esophageal temperatures.     

Effect of expiratory muscle fatigue on exercise tolerance and locomotor muscle fatigue in healthy humans

High-intensity exercise (> or =90% of maximal O(2) uptake) sustained to the limit of tolerance elicits expiratory muscle fatigue (EMF). We asked whether prior EMF affects subsequent exercise tolerance. Eight male subjects (means +/- SD; maximal O(2) uptake = 53.5 +/- 5.2 ml.kg(-1).min(-1)) cycled at 90% of peak power output to the limit of tolerance with (EMF-EX) and without (CON-EX) prior induction of EMF and for a time equal to that achieved in EMF-EX but without prior induction of EMF (ISO-EX). To induce EMF, subjects breathed against an expiratory flow resistor until task failure (15 breaths/min, 0.7 expiratory duty cycle, 40% of maximal expiratory gastric pressure). Fatigue of abdominal and quadriceps muscles was assessed by measuring the reduction relative to prior baseline values in magnetically evoked gastric twitch pressure (Pga(tw)) and quadriceps twitch force (Q(tw)), respectively. The reduction in Pga(tw) was not different after resistive breathing vs. after CON-EX (-27 +/- 5 vs. -26 +/- 6%; P = 0.127). Exercise time was reduced by 33 +/- 10% in EMF-EX vs. CON-EX (6.85 +/- 2.88 vs. 9.90 +/- 2.94 min; P < 0.001). Exercise-induced abdominal and quadriceps muscle fatigue was greater after EMF-EX than after ISO-EX (-28 +/- 9 vs. -12 +/- 5% for Pga(tw), P = 0.001; -28 +/- 7 vs. -14 +/- 6% for Q(tw), P = 0.015). Perceptual ratings of dyspnea and leg discomfort (Borg CR10) were higher at 1 and 3 min and at end exercise during EMF-EX vs. during ISO-EX (P < 0.05). Percent changes in limb fatigue and leg discomfort (EMF-EX vs. ISO-EX) correlated significantly with the change in exercise time. We propose that EMF impaired subsequent exercise tolerance primarily through an increased severity of limb locomotor muscle fatigue and a heightened perception of leg discomfort.     

Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise.

Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle training, 30 min/day, 6 days/wk for 10 wk at approximately 70% of maximal O(2) uptake) and untrained (UT) legs of healthy men (H) [n = 6, age 60 +/- 2 (SE) yr] and patients with Type 2 diabetes mellitus (DM) (n = 4, age 56 +/- 3 yr) during a hyperinsulinemic ( approximately 16,000 pmol/l), isoglycemic clamp with a final 30 min of superimposed two-legged exercise at 70% of individual maximal heart rate. With superimposed exercise, leg glucose extraction decreased (P < 0.05), and leg blood flow and leg glucose clearance increased (P < 0.05), compared with hyperinsulinemia alone. During exercise, leg blood flow was similar in both groups of subjects and between T and UT legs, whereas glucose extraction was always higher (P < 0.05) in T compared with UT legs (15.8 +/- 1.2 vs. 14.6 +/- 1.8 and 11.9 +/- 0.8 vs. 8.8 +/- 1.8% for H and DM, respectively) and leg glucose clearance was higher in T (H: 73 +/- 8, DM: 70 +/- 10 ml. min(-1). kg leg(-1)) compared with UT (H: 63 +/- 8, DM: 45 +/- 7 ml. min(-1). kg leg(-1)) but not different between groups (P > 0.05). From these results it can be concluded that, in both diabetic and healthy aged muscle, exercise adds to a maximally insulin-stimulated glucose clearance and that glucose extraction and clearance are both enhanced by training.     

Effects of "priming" exercise on pulmonary O2 uptake and muscle deoxygenation kinetics during heavy-intensity cycle exercise in the supine and upright positions.

We hypothesized that the performance of prior heavy exercise would speed the phase 2 oxygen consumption (VO2) kinetics during subsequent heavy exercise in the supine position (where perfusion pressure might limit muscle O2 supply) but not in the upright position. Eight healthy men (mean +/- SD age 24 +/- 7 yr; body mass 75.0 +/- 5.8 kg) completed a double-step test protocol involving two bouts of 6 min of heavy cycle exercise, separated by a 10-min recovery period, on two occasions in each of the upright and supine positions. Pulmonary O2 uptake was measured breath by breath and muscle oxygenation was assessed using near-infrared spectroscopy (NIRS). The NIRS data indicated that the performance of prior exercise resulted in hyperemia in both body positions. In the upright position, prior exercise had no significant effect on the time constant tau of the VO2 response in phase 2 (bout 1: 29 +/- 10 vs. bout 2: 28 +/- 4 s; P = 0.91) but reduced the amplitude of the VO2 slow component (bout 1: 0.45 +/- 0.16 vs. bout 2: 0.22 +/- 0.14 l/min; P = 0.006) during subsequent heavy exercise. In contrast, in the supine position, prior exercise resulted in a significant reduction in the phase 2 tau (bout 1: 38 +/- 18 vs. bout 2: 24 +/- 9 s; P = 0.03) but did not alter the amplitude of the VO2 slow component (bout 1: 0.40 +/- 0.29 vs. bout 2: 0.41 +/- 0.20 l/min; P = 0.86). These results suggest that the performance of prior heavy exercise enables a speeding of phase 2 VO2 kinetics during heavy exercise in the supine position, presumably by negating an O2 delivery limitation that was extant in the control condition, but not during upright exercise, where muscle O2 supply was probably not limiting.     

Influence of physical training on heart rate variability and baroreflex circulatory control

Nineteen males (aged 45-68 yr) were studied before and after either a period of regular endurance exercise [walk/jog 3-4 days/wk for 30 +/- 1 (SE) wk, n = 11] or unchanged physical activity (38 +/- 2 wk, n = 8) (controls) to determine the influence of physical training on cardiac parasympathetic (vagal) tone and baroreflex control of heart rate (HR) and limb vascular resistance (VR) at rest in middle-aged and older men. Training resulted in a marked increase in maximal O2 uptake (31.6 +/- 1.2 vs. 41.0 +/- 1.8 ml.kg-1.min-1, 2.56 +/- 0.16 vs. 3.20 +/- 0.18 l/min, P less than 0.05) and small (P less than 0.05) reductions in body weight (81.2 +/- 3.5 vs. 78.7 +/- 4.0 kg) and body fat (23.8 +/- 1.3 vs. 20.9 +/- 1.3%). HR at rest was slightly, but consistently, lower after training (63 +/- 2 vs. 58 +/- 1 beats/min, P less than 0.05). In general, HR variability (index of cardiac vagal tone) was greater after training. Chronotropic responsiveness to either brief carotid baroreflex stimulation (neck suction) or inhibition (neck pressure), or to non-specific arterial baroreflex inhibition induced by a hypotensive level of lower body suction, was unchanged after training. In contrast, the magnitude of the reflex increase in forearm VR in response to three levels of lower body suction was markedly attenuated after training (38-59%; P less than 0.05 at -10 and -30 mmHg; P = 0.07 at -20 mmHg). None of these variables or responses was altered over time in the controls. These findings indicate that in healthy, previously sedentary, middle-aged and older men, strenuous and prolonged endurance training 1) elicits large increases in maximal exercise capacity and small reductions in HR at rest, 2) may increase cardiac vagal tone at rest, 3) does not alter arterial baroreflex control of HR, and 4) results in a diminished forearm vasoconstrictor response to reductions in baroreflex sympathoinhibition.     

Impaired endothelium-mediated vasodilation is not the principal cause of vasoconstriction in heart failure

The extent to which abnormal endothelium-dependent vasodilator mechanisms contribute to abnormal resting vasoconstriction and blunted reflex vasodilation seen in heart failure is unknown. The purpose of this study was to test the hypothesis that the resting and reflex abnormalities in vascular tone that characterize heart failure are mediated by abnormal endothelium-mediated mechanisms. Thirteen advanced heart-failure patients (New York Heart Association III-IV) and 13 age-matched normal controls were studied. Saline, acetylcholine (20 microg/min), or L-arginine (10 mg/min) was infused into the brachial artery, and forearm blood flow was measured by venous plethysmography at rest and during mental stress. At rest, acetylcholine decreased forearm vascular resistance in normal subjects, but this response was blunted in heart failure. During mental stress with intra-arterial acetylcholine or L-arginine, the decrease in forearm vascular resistance was not greater than during saline control in heart failure [saline control vs. acetylcholine (7 +/- 3 vs. 6 +/- 3, P = NS) or vs. L-arginine (9 +/- 2 units, P = NS)]. The increase in forearm blood flow was not greater than during saline control in heart failure [saline control vs. acetylcholine (1. 2 +/- 0.3 vs. 1.3 +/- 0.3, P = NS), or vs. L-arginine (1.2 +/- 0.2 ml x min(-1) x 100 ml(-1), P = NS)]. Furthermore, during mental stress with nitroprusside, the decrease in forearm vascular resistance was not greater than during saline control [saline control vs. nitroprusside (7 +/- 3 vs. 5 +/- 4 ml x min(-1) x 100 g(-1), P = NS)], and the increase in forearm blood flow was not greater than during saline control [saline control vs. nitroprusside (1.2 +/- 0.3 vs. 1.3 +/- 0.5 ml x min(-1) x 100 g(-1), P = NS)]. Because the endothelial-independent agent nitroprusside was unable to restore resting and reflex vasodilation to normal in heart failure, we conclude that impaired endothelium-mediated vasodilation with acetylholine-nitric oxide cannot be the principal cause of the attenuated resting- or reflex-mediated vasodilation in heart failure.     

Total nitrogen oxide following exercise testing reflects endothelial function and discriminates health status

Nitric oxide (NO) bioavailability is important in vascular health, but unsuitable as a clinical measure due to biological oxidation. Total nitrogen oxides (NO(x)) are stable but background nitrate levels make it difficult to detect disease-based variation. We investigated the clinical discriminatory value of NO(x) as it relates to exercise capability (VO(2peak)) and brachial artery reactivity (BAR, an NO-dependent measure of endothelial health), in healthy (H), increased risk (RF), and known cardiovascular disease (CVD) subjects. BAR was measured using forearm occlusion/hyperemia stimulus. Subjects performed a maximal graded exercise test (GXT). Blood at rest, exercise termination, and 10 min into recovery was mixed equally with 0.1 M NaOH at 4 degrees C, filtered, and stored at -70 degrees C. NO(x) was measured by chemiluminescence. Seven of the RF group then exercise-trained for 6 months prior to retesting. The H group (n = 12) was younger, had higher VO(2peak), HDL levels, and baseline NO(x) values than the RF (n = 15) and CVD (n = 10) groups. NO(x) increased from baseline to recovery in the H group only (75.85 +/- 19.04 microM vs 97.76 +/- 31.93 microM; P 相似文献   

Hypoxia potentiates exercise-induced sympathetic neural activation in humans.

Our purpose was to test the hypothesis that hypoxia potentiates exercise-induced sympathetic neural activation in humans. In 15 young (20-30 yr) healthy subjects, lower leg muscle sympathetic nerve activity (MSNA, peroneal nerve; microneurography), venous plasma norepinephrine (PNE) concentrations, heart rate, and arterial blood pressure were measured at rest and in response to rhythmic handgrip exercise performed during normoxia or isocapnic hypoxia (inspired O2 concn of 10%). Study I (n = 7): Brief (3-4 min) hypoxia at rest did not alter MSNA, PNE, or arterial pressure but did induce tachycardia [17 +/- 3 (SE) beats/min; P less than 0.05]. During exercise at 50% of maximum, the increases in MSNA (346 +/- 81 vs. 207 +/- 14% of control), PNE (175 +/- 25 vs. 120 +/- 11% of control), and heart rate (36 +/- 2 vs. 20 +/- 2 beats/min) were greater during hypoxia than during normoxia (P less than 0.05), whereas the arterial pressure response was not different (26 +/- 4 vs. 25 +/- 4 mmHg). The increase in MSNA during hypoxic exercise also was greater than the simple sum of the separate responses to hypoxia and normoxic exercise (P less than 0.05). Study II (n = 8): In contrast to study I, during 2 min of exercise (30% max) performed under conditions of circulatory arrest and 2 min of postexercise circulatory arrest (local ischemia), the MSNA and PNE responses were similar during systemic hypoxia and normoxia. Arm ischemia without exercise had no influence on any variable during hypoxia or normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of short-term diet and exercise on insulin action in individuals with abnormal glucose tolerance.

The effects of a 10-day low-calorie diet (LCD; n = 8) or exercise training (ET; n = 8) on insulin secretion and action were compared in obese men (n = 9) and women (n = 7), aged 53 +/- 1 yr, with abnormal glucose tolerance by using a hyperglycemic clamp with superimposed arginine infusion and a high-fat drink. Body mass (LCD, 115 +/- 5 vs. 110 +/- 5 kg; ET, 111 +/- 7 vs. 109 +/- 7 kg; P < 0. 01) and fasting plasma glucose (LCD, 115 +/- 10 vs. 99 +/- 4 mg/dl; ET, 112 +/- 4 vs. 101 +/- 5 mg/dl, P < 0.01) and insulin (LCD, 23.9 +/- 5.6 vs. 15.2 +/- 3.9 microU/ml; ET, 17.6 +/- 1.9 vs. 13.9 +/- 2. 4 microU/ml; P < 0.05) decreased in both groups. There was a 40% reduction in plasma insulin during hyperglycemia (0-45 min) after LCD (peak: 118 +/- 18 vs. 71 +/- 14 microU/ml; P < 0.05) and ET (69 +/- 14 vs. 41 +/- 7 microU/ml; P < 0.05) and trends for reductions during arginine infusion and a high-fat drink. The 56% increase in glucose uptake after ET (4.95 +/- 0.90 vs. 7.74 +/- 0.82 mg. min-1. kg fat-free mass-1; P < 0.01) was significantly (P < 0.01) greater than the 19% increase (5.72 +/- 1.12 vs. 6.80 +/- 0.94 mg. min-1. kg fat-free mass-1; P = not significant) that occurred after LCD. The marked increase in glucose disposal after ET, despite lower insulin levels, suggests that short-term exercise is more effective than diet in enhancing insulin action in individuals with abnormal glucose tolerance.