Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia.

Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 +/- 1 vs. 36 +/- 2 bursts/min, 1.8 +/- 0.1 vs. 2.2 +/- 0.2 ml.min(-1).100 ml(-1), 89 +/- 2 vs. 92 +/- 2 mmHg, and 58 +/- 1 vs. 62 +/- 1 beats/min, respectively, P < 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 +/- 2 vs. 31 +/- 2 bursts/min), and FBF was significantly higher (2.2 +/- 0.2 vs. 1.8 +/- 0.1 ml.min(-1).100 ml(-1), P < 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.     

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.     

Exercise pressor reflex in humans with end-stage renal disease

Previous work has suggested that end-stage renal disease (ESRD) patients may have an exaggerated sympathetic nervous system (SNS) response during exercise. We hypothesized that ESRD patients have an exaggerated blood pressure (BP) response during moderate static handgrip exercise (SHG 30%) and that the exaggerated BP response is mediated by SNS overactivation, characterized by augmented mechanoreceptor activation and blunted metaboreceptor control, as has been described in other chronic diseases. We measured hemodynamics and muscle sympathetic nerve activity (MSNA) in 13 ESRD and 16 controls during: 1) passive hand movement (PHM; mechanoreceptor isolation); 2) low-level rhythmic handgrip exercise (RHG 20%; central command and mechanoreceptor activation); 3) SHG 30%, followed by posthandgrip circulatory arrest (PHGCA; metaboreceptor activation); and 4) cold pressor test (CPT; nonexercise stimulus). ESRD patients had exaggerated increases in systolic BP during SHG 30%; however, the absolute and relative increase in MSNA was not augmented, excluding SNS overactivation as the cause of the exaggerated BP response. Increase in MSNA was not exaggerated during RHG 20% and PHM, demonstrating that mechanoreceptor activation is not heightened in ESRD. During PHGCA, MSNA remained elevated in controls but decreased rapidly to baseline levels in ESRD, indicative of markedly blunted metaboreceptor control of MSNA. MSNA response to CPT was virtually identical in ESRD and controls, excluding a generalized sympathetic hyporeactivity in ESRD. In conclusion, ESRD patients have an exaggerated increase in SBP during SHG 30% that is not mediated by overactivation of the SNS directed to muscle. SBP responses were also exaggerated during mechanoreceptor activation and metaboreceptor activation, but without concomitant augmentation in MSNA responses. Metaboreceptor control of MSNA was blunted in ESRD, but the overall ability to mount a SNS response was not impaired. Other mechanisms besides SNS overactivation, such as impaired vasodilatation, should be explored to explain the exaggerated exercise pressor reflex in ESRD.     

Seven days of aerobic exercise training improves conduit artery blood flow following glucose ingestion in patients with type 2 diabetes

The vasodilatory effects of insulin account for up to 40% of insulin-mediated glucose disposal; however, insulin-stimulated vasodilation is impaired in individuals with type 2 diabetes, limiting perfusion and delivery of glucose and insulin to target tissues. To determine whether exercise training improves conduit artery blood flow following glucose ingestion, a stimulus for increasing circulating insulin, we assessed femoral blood flow (FBF; Doppler ultrasound) during an oral glucose tolerance test (OGTT; 75 g glucose) in 11 overweight or obese (body mass index, 34 ± 1 kg/m2), sedentary (peak oxygen consumption, 23 ± 1 ml·kg?1·min?1) individuals (53 ± 2 yr) with non-insulin-dependent type 2 diabetes (HbA1c, 6.63 ± 0.18%) before and after 7 days of supervised treadmill and cycling exercise (60 min/day, 60-75% heart rate reserve). Fasting glucose, insulin, and FBF were not significantly different after 7 days of exercise, nor were glucose or insulin responses to the OGTT. However, estimates of whole body insulin sensitivity (Matsuda insulin sensitivity index) increased (P < 0.05). Before exercise training, FBF did not change significantly during the OGTT (1 ± 7, -7 ± 5, 0 ± 6, and 0 ± 5% of fasting FBF at 75, 90, 105, and 120 min, respectively). In contrast, after exercise training, FBF increased by 33 ± 9, 39 ± 14, 34 ± 7, and 48 ± 18% above fasting levels at 75, 90, 105, and 120 min, respectively (P < 0.05 vs. corresponding preexercise time points). Additionally, postprandial glucose responses to a standardized breakfast meal consumed under "free-living" conditions decreased during the final 3 days of exercise (P < 0.05). In conclusion, 7 days of aerobic exercise training improves conduit artery blood flow during an OGTT in individuals with type 2 diabetes.     

Hyperoxia enhances metaboreflex sensitivity during static exercise in humans

Peripheral chemoreflex inhibition with hyperoxia decreases sympathetic nerve traffic to muscle circulation [muscle sympathetic nerve activity (MSNA)]. Hyperoxia also decreases lactate production during exercise. However, hyperoxia markedly increases the activation of sensory endings in skeletal muscle in animal studies. We tested the hypothesis that hyperoxia increases the MSNA and mean blood pressure (MBP) responses to isometric exercise. The effects of breathing 21% and 100% oxygen at rest and during isometric handgrip at 30% of maximal voluntary contraction on MSNA, heart rate (HR), MBP, blood lactate (BL), and arterial O2 saturation (SaO2) were determined in 12 healthy men. The isometric handgrips were followed by 3 min of postexercise circulatory arrest (PE-CA) to allow metaboreflex activation in the absence of other reflex mechanisms. Hyperoxia lowered resting MSNA, HR, MBP, and BL but increased Sa(O2) compared with normoxia (all P < 0.05). MSNA and MBP increased more when exercise was performed in hyperoxia than in normoxia (MSNA: hyperoxic exercise, 255 +/- 100% vs. normoxic exercise, 211 +/- 80%, P = 0.04; and MBP: hyperoxic exercise, 33 +/- 9 mmHg vs. normoxic exercise, 26 +/- 10 mmHg, P = 0.03). During PE-CA, MSNA and MBP remained elevated (both P < 0.05) and to a larger extent during hyperoxia than normoxia (P < 0.05). Hyperoxia enhances the sympathetic and blood pressure (BP) reactivity to metaboreflex activation. This is due to an increase in metaboreflex sensitivity by hyperoxia that overrules the sympathoinhibitory and BP lowering effects of chemoreflex inhibition. This occurs despite a reduced lactic acid production.     

Enhancement of vascular function mediated by insulin and insulin-like growth factor-1 following single exercise session

Exercise is well-known in improving vascular functions, but the underlying mechanism has not been totally understood. The aim of this study was to examine whether single exercise session acutely enhances insulin-induced and insulin-like growth factor-1 (IGF-1)-induced vasorelaxation. Twenty-four male Wistar rats at age of 12 weeks were randomly divided into two groups, control (n = 12) and exercise (n = 12) group. The exercise group ran on a treadmill at a speed of 18 m/min for 60 min. Immediately after exercise, insulin-induced and IGF-1-induced vasorelaxant responses were evaluated by the isometric tension of aortic rings in the organ baths. The roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS) in vasorelaxant responses were examined by treating selective inhibitors, such as wortmannin (an inhibitor of PI3K) and N(omega)-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). In addition, the vascular responses to sodium nitroprusside (SNP), a NO donor, were examined. We found that single exercise session significantly enhanced vasorelaxation mediated by insulin and IGF-1 in rat aortas (P < 0.01). Also, the exercise-enhanced vasorelaxation was abolished by wortmannin or L-NAME. There was no significant difference of SNP-induced vasorelaxation between control and exercise groups. These results indicate that single exercise session acutely enhances insulin-induced and IGF-1-induced vasorelaxation through the PI3K-NOS-dependent pathway.     

Skeletal muscle contraction stimulates capillary recruitment and glucose uptake in insulin-resistant obese Zucker rats

Exercise and insulin increase muscle glucose uptake by different mechanisms and also increase capillary recruitment, which is proposed to facilitate access for hormones and nutrients. The genetically obese Zucker rat shows impaired insulin- but not contraction-mediated glucose uptake in muscle. Recently, we have shown the genetically obese Zucker rats to have impaired insulin-mediated capillary recruitment and proposed that this contributes to the insulin resistance of muscle in vivo. Because this might imply a general loss of recruitable capillaries, we now assess responses to contraction in muscles of 18 +/- 3-wk-old lean and obese Zucker rats in vivo. Field stimulation (2 Hz, 0.1 ms) was conducted for 1 h on one leg of anesthetized instrumented rats, and measurements were made of femoral blood flow (FBF), heart rate (HR), blood pressure (BP), hindleg metabolism of 1-methylxanthine (a measure of capillary recruitment), hindleg glucose uptake (HGU), and lower leg muscle glucose uptake by 2-deoxyglucose (R'g). Lean animals (311 +/- 9 g) developed tension at 219 +/- 27 g/g muscle with no change in BP but with significant increases in HR, FBF, HGU, 1-MX metabolism, and R'g (P < 0.05), compared with nonstimulated control leans. Obese animals (469 +/- 7 g) developed tension at 265 +/- 31 g/g muscle with no change in HR or BP but with significant increases in FBF, HGU, 1-MX metabolism, and R'g (P < 0.05) compared with nonstimulated control obese rats. Muscle contraction of lean animals led to a greater increase in lower leg R'g, similar responses in HGU and 1-MX, and a smaller increase in FBF than in obese animals. A tight correlation between FBF and capillary recruitment was noted for all data (P < 0.001). It is concluded that contraction-mediated muscle capillary recruitment and glucose uptake are essentially normal in the obese Zucker rat and that control of FBF and capillary recruitment in exercise is closely linked.     

Differential Impact of Acute High-Intensity Exercise on Circulating Endothelial Microparticles and Insulin Resistance between Overweight/Obese Males and Females

BackgroundAn acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women.MethodsInactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E⁺ and CD31⁺/CD42b^- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR).ResultsThere was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all P<0.05). In males, both HICE and HIIE reduced EMPs compared to Control (P≤0.05). In females, HICE increased CD62E+ EMPs (P<0.05 vs. Control) whereas CD31+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05).ConclusionsOverweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females.     

Chemoreflex and metaboreflex control during static hypoxic exercise

To investigate the effects of muscle metaboreceptor activation during hypoxic static exercise, we recorded muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, ventilation, and blood lactate in 13 healthy subjects (22 +/- 2 yr) during 3 min of three randomized interventions: isocapnic hypoxia (10% O(2)) (chemoreflex activation), isometric handgrip exercise in normoxia (metaboreflex activation), and isometric handgrip exercise during isocapnic hypoxia (concomitant metaboreflex and chemoreflex activation). Each intervention was followed by a forearm circulatory arrest to allow persistent metaboreflex activation in the absence of exercise and chemoreflex activation. Handgrip increased blood pressure, MSNA, heart rate, ventilation, and lactate (all P < 0.001). Hypoxia without handgrip increased MSNA, heart rate, and ventilation (all P < 0.001), but it did not change blood pressure and lactate. Handgrip enhanced blood pressure, heart rate, MSNA, and ventilation responses to hypoxia (all P < 0.05). During circulatory arrest after handgrip in hypoxia, heart rate returned promptly to baseline values, whereas ventilation decreased but remained elevated (P < 0.05). In contrast, MSNA, blood pressure, and lactate returned to baseline values during circulatory arrest after hypoxia without exercise but remained markedly increased after handgrip in hypoxia (P < 0.05). We conclude that metaboreceptors and chemoreceptors exert differential effects on the cardiorespiratory and sympathetic responses during exercise in hypoxia.     

Sweating and skin blood flow during exercise: effects of age and maximal oxygen uptake

Individuals greater than or equal to 60 yr of age are more susceptible to hyperthermia than younger people. However, the mechanisms involved remain unclear. To gain further insight, we examined the heat loss responses of 7 young (24-30 yr) and 13 older (58-74 yr) men during 20 min of cycle exercise [67.5% maximal O2 uptake (VO2max)] in a warm environment (30 degrees C, 55% relative humidity). Forearm blood flow (FBF) and chest sweat rate (SR) were plotted as a function of the weighted average of mean skin and esophageal temperatures [Tes(w)] during exercise. The sensitivity and threshold for each response were defined as the slope and Tes(w) at the onset of the response, respectively. When the young sedentary men were compared with a subgroup (n = 7) of the older physically active men with similar VO2max, the SR and FBF responses of the two groups did not differ significantly. However, when the young men were compared with a subgroup of older sedentary men with a similar maximal O2 pulse, the SR and FBF sensitivities were significantly reduced by 62 and 40%, respectively. These findings suggest that during a short exercise bout either 1) there is no primary effect of aging on heat loss responses but, rather, changes are associated with the age-related decrease in VO2max or 2) the decline in heat loss responses due to aging may be masked by repeated exercise training.     

Exercise intensity and glucose tolerance in trained and nontrained subjects

The improved glucose tolerance and increased insulin sensitivity associated with regular exercise appear to be the result, in large part, of the residual effects of the last bout of exercise. To determine the effects of exercise intensity on this response, glucose tolerance and the insulin response to a glucose load were determined in seven well-trained male subjects [maximal O2 uptake (VO2max) = 58 ml.kg-1.min-1] and in seven nontrained male subjects (VO2max = 49 ml.kg-1.min-1) in the morning after an overnight fast 1) 40 h after the last training session (control), 2) 14 h after 40 min of exercise on a cycle ergometer at 40% VO2max, and 3) 14 h after 40 min of exercise at 80% VO2max. Subjects replicated their diets for 3 days before each test and ate a standard meal the evening before the oral glucose tolerance test. No differences in the 3-h insulin or glucose response were observed between the control trial and before exercise at either 40 or 80% VO2max in the trained subjects. In the nontrained subjects the plasma insulin response was decreased by 40% after a single bout of exercise at either 40 or 80% VO2max (7.0 X 10(3) vs. 5.0 X 10(3), P less than 0.05; 3.8 X 10(3) microU.ml-1.180 min-1, P less than 0.01). The insulin response after a single bout of exercise in the nontrained subjects was comparable with the insulin responses found in the trained subjects for the control and exercise trials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the alpha index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2 to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1 ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.     

Inspiratory muscle fatigue increases sympathetic vasomotor outflow and blood pressure during submaximal exercise

The purpose of this study was to elucidate the influence of inspiratory muscle fatigue on muscle sympathetic nerve activity (MSNA) and blood pressure (BP) response during submaximal exercise. We hypothesized that inspiratory muscle fatigue would elicit increases in sympathetic vasoconstrictor outflow and BP during dynamic leg exercise. The subjects carried out four submaximal exercise tests: two were maximal inspiratory pressure (PI(max)) tests and two were MSNA tests. In the PI(max) tests, the subjects performed two 10-min exercises at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and with or without inspiratory resistive breathing for 5 min (breathing frequency: 60 breaths/min, inspiratory and expiratory times were each set at 0.5 s)]. Before and immediately after exercise, PI(max) was estimated. In MSNA tests, the subjects performed two 15-min exercises (spontaneous breathing for 5 min, with or without inspiratory resistive breathing for 5 min, and spontaneous breathing for 5 min). MSNA was recorded via microneurography of the right median nerve at the elbow. PI(max) decreased following exercise with resistive breathing, whereas no change was found without resistance. The time-dependent increase in MSNA burst frequency (BF) appeared during exercise with inspiratory resistive breathing, accompanied by an augmentation of diastolic BP (DBP) (with resistance: MSNA, BF +83.4%; DBP, +23.8%; without resistance: MSNA BF, +19.2%; DBP, -0.4%, from spontaneous breathing during exercise). These results suggest that inspiratory muscle fatigue induces increases in muscle sympathetic vasomotor outflow and BP during dynamic leg exercise at mild intensity.     

Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle

Exercise enhances insulin sensitivity in skeletal muscle, but the underlying mechanism remains obscure. Recent data suggest that alternatively activated M2 macrophages enhance insulin sensitivity in insulin target organs such as adipose tissue and liver. Therefore, the aim of this study was to determine the role of anti-inflammatory M2 macrophages in exercise-induced enhancement of insulin sensitivity in skeletal muscle. C57BL6J mice underwent a single bout of treadmill running (20 m/min, 90 min). Twenty-four hours later, ex vivo insulin-stimulated 2-deoxy glucose uptake was found to be increased in plantaris muscle. This change was associated with increased number of CD163-expressing macrophages (i.e. M2-polarized macrophages) in skeletal muscle. Systemic depletion of macrophages by pretreatment of mice with clodronate-containing liposome abrogated both CD163-positive macrophage accumulation in skeletal muscle as well as the enhancement of insulin sensitivity after exercise, without affecting insulin-induced phosphorylation of Akt and AS160 or exercise-induced GLUT4 expression. These results suggest that accumulation of M2-polarized macrophages is involved in exercise-induced enhancement of insulin sensitivity in mouse skeletal muscle, independently of the phosphorylation of Akt and AS160 and expression of GLUT4.     

Evaluation of muscle metaboreflex function through graded reduction in forearm blood flow during rhythmic handgrip exercise in humans

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Our aim was to determine the muscle metaboreflex threshold and gain in humans by creating an open-loop relationship between active muscle blood flow and hemodynamic responses during a rhythmic handgrip exercise. Eleven healthy subjects performed the exercise at 5 or 15% of maximal voluntary contraction (MVC) in random order. During the exercise, forearm blood flow (FBF), which was continuously measured using Doppler ultrasound, was reduced in five steps by manipulating the inner pressure of an occlusion cuff on the upper arm. The FBF at each level was maintained for 3 min. The initial reductions in FBF elicited no hemodynamic changes, but once FBF fell below a threshold, mean arterial blood pressure (MAP) and heart rate (HR) increased and total vascular conductance (TVC) decreased in a linear manner. The threshold FBF during the 15% MVC trial was significantly higher than during the 5% MVC trial. The gain was then estimated as the slope of the relationship between the hemodynamic responses and FBFs below the threshold. The gains for the MAP and TVC responses did not differ between workloads, but the gain for the HR response was greater in the 15% MVC trial. Our findings thus indicate that increasing the workload shifts the threshold for the muscle metaboreflex to higher blood flows without changing the gain of the reflex for the MAP and TVC responses, whereas it enhances the gain for the HR response.     

Interstitial pH, K(+), lactate, and phosphate determined with MSNA during exercise in humans

The purpose of the present study was to use the microdialysis technique to simultaneously measure the interstitial concentrations of several putative stimulators of the exercise pressor reflex during 5 min of intermittent static quadriceps exercise in humans (n = 7). Exercise resulted in approximately a threefold (P < 0.05) increase in muscle sympathetic nerve activity (MSNA) and 13 +/- 3 beats/min (P < 0.05) and 20 +/- 2 mmHg (P < 0.05) increases in heart rate and blood pressure, respectively. During recovery, all reflex responses quickly returned to baseline. Interstitial lactate levels were increased (P < 0.05) from rest (1.1 +/- 0.1 mM) to exercise (1. 6 +/- 0.2 mM) and were further increased (P < 0.05) during recovery (2.0 +/- 0.2 mM). Dialysate phosphate concentrations were 0.55 +/- 0. 04, 0.71 +/- 0.05, and 0.48 +/- 0.03 mM during rest, exercise, and recovery, respectively, and were significantly elevated during exercise. At the onset of exercise, dialysate K(+) levels rose rapidly above resting values (4.2 +/- 0.1 meq/l) and continued to increase during the exercise bout. After 5 min of contractions, dialysate K(+) levels had peaked with an increase (P < 0.05) of 0.6 +/- 0.1 meq/l and subsequently decreased during recovery, not being different from rest after 3 min. In contrast, H(+) concentrations rapidly decreased (P < 0.05) from resting levels (69.4 +/- 3.7 nM) during quadriceps exercise and continued to decrease with a mean decline (P < 0.05) of 16.7 +/- 3.8 nM being achieved after 5 min. During recovery, H(+) concentrations rapidly increased and were not significantly different from baseline after 1 min. This study represents the first time that skeletal muscle interstitial pH, K(+), lactate, and phosphate have been measured in conjunction with MSNA, heart rate, and blood pressure during intermittent static quadriceps exercise in humans. These data suggest that interstitial K(+) and phosphate, but not lactate and H(+), may contribute to the stimulation of the exercise pressor reflex.     

Neurovascular responses to mental stress in the supine and upright postures.

The purpose of this study was to determine neurovascular responses to mental stress (MS) in the supine and upright postures. MS was elicited in 23 subjects (26 +/- 1 yr) by 5 min of mental arithmetic. In study 1 (n = 9), Doppler ultrasound was used to measure mean blood flow velocity in the renal (RBFV) and superior mesenteric arteries (SMBFV), and venous occlusion plethysmography was used to measure forearm blood flow (FBF). In study 2 (n = 14), leg blood flow (LBF; n = 9) was measured by Doppler ultrasound, and muscle sympathetic nerve activity (MSNA; n = 5) was measured by microneurography. At rest, upright posture increased heart rate and MSNA and decreased LBF, FBF, RBFV, and SMBFV and their respective conductances. MS elicited similar increases in mean arterial blood pressure ( approximately 12 mmHg) and heart rate ( approximately 17 beats/min), regardless of posture. MS in both postures elicited a decrease in RBFV, SMBFV, and their conductances and an increase in LBF, FBF, and their conductances. Changes in blood flow were blunted in the upright posture in all vascular beds examined, but the pattern of the vascular response was the same as the supine posture. MS did not change MSNA in either posture (change: approximately 1 +/- 3 and approximately 3 +/- 3 bursts/min, respectively). In conclusion, the augmented sympathetic activity of the upright posture does not alter heart rate, mean arterial blood pressure, or MSNA responses to MS. MS elicits divergent vascular responses in the visceral and peripheral vasculature. These results indicate that, although the upright posture attenuates vascular responses to MS, the pattern of neurovascular responses does not differ between postures.     

Arterial baroreflex control of muscle sympathetic nerve activity in the transition from rest to steady-state dynamic exercise in humans

We sought to investigate arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) in the transition from rest to steady-state dynamic exercise. This was accomplished by assessing the relationship between spontaneous variations in diastolic blood pressure (DBP) and MSNA at rest and during the time course of reaching steady-state arm cycling at 50% peak oxygen uptake (VO(2peak)). Specifically, DBP-MSNA relations were examined in eight subjects (25 +/- 1 yr) at the start of unloaded arm cycling and then during the initial and a later period of arm cycling once the 50% VO(2peak) work rate was achieved. Heart rate and arterial blood pressure were progressively increased throughout exercise. Although resting MSNA [16 +/- 2 burst/min; 181 +/- 36 arbitrary units (au) total activity] was unchanged during unloaded cycling, MSNA burst frequency and total activity were significantly elevated during the initial (27 +/- 4 burst/min; 367 +/- 76 au; P < 0.05) and later (36 +/- 7 burst/min; 444 +/- 91 au; P < 0.05) periods of exercise. The relationships between DBP and burst incidence, burst strength, and total MSNA were progressively shifted rightward from unloaded to the initial to the later period of 50% VO(2peak) arm cycling without any changes in the slopes of the linear regressions (i.e., ABR sensitivity). Thus a continuous and dynamic resetting of the ABR control of MSNA occurred during the transition from rest to steady-state dynamic exercise. These findings indicate that the ABR control of MSNA was well maintained throughout dynamic exercise in humans, progressively being reset to operate around the exercise-induced elevations in blood pressure and MSNA without any changes in reflex sensitivity.     

Lack of effects of an acute hepatic vagotomy on insulin and catecholamine responses in rats following exercise

The purpose of the present investigation was to evaluate the effects of an acute hepatic vagotomy on hormonal responses to hyperglycemic and hypoglycemic challenges in rats previously submitted to an exercise protocol. Two experiments were conducted. In a first experiment, 8-week trained (TR) and untrained (UNTR) rats, subdivided into acutely hepatic vagotomized (HV) and sham-operated (SHM) groups, were submitted to an intraperitoneal glucose tolerance test (0.5 g/kg) under anesthesia. Training was associated with a tendency (P = 0.07) for blood glucose levels to be less elevated (at time point 10 min), and with a significant (P < 0.01) lower glucose/insulin ratio following the glucose injection. The HV did not have any effects on these responses. In a second experiment, non-exercised rats and a group of rats submitted to an acute bout of exercise (treadmill, 60 min, 26 m/min, 5% slope) 24 h before the experiment, each one of these two groups being subdivided into acutely HV and SHM groups, were submitted to an insulin-induced hypoglycemia protocol, under anesthesia. Blood glucose concentrations were decreased significantly (P < 0.01) to approximately 40 mg/dl in all groups 60 and 80 min after the insulin injection. Plasma adrenaline and noradrenaline levels were increased significantly (P < 0.01) in all groups. The catecholamine increase was not influenced by the HV or the acute exercise bout. The present results do not indicate an implication of the hepatic vagus nerve on hormonal responses to hyper and hypoglycemia following exercise.     

Venous occlusion to the lower limb attenuates vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia.

We investigated the effects of increases in calf volume on cardiovascular responses during handgrip (HG) exercise and post-HG exercise muscle ischemia (PEMI). Seven subjects completed two trials: one control (no occlusion) and one venous occlusion (VO) session. Both trials included a baseline measurement followed by 15 min of rest (REST), 2 min of HG, and 2 min of PEMI. VO was applied at 100 mmHg via cuffs placed around both distal thighs during REST, HG, and PEMI. Mean arterial pressure, heart rate, forearm blood flow (FBF) in the nonexercised arm, and forearm vascular resistance (FVR) in the nonexercised arm (FVR) were measured. During REST and HG, there were no significant differences between trials in all parameters. During PEMI in the control trial, mean arterial pressure and FVR were significantly greater and FBF was significantly lower than baseline values (P < 0.05 for each). In contrast, in the VO trial, FBF and FVR responses were different from control responses. In the VO trial, FBF was significantly greater than in the control trial (4.7 +/- 0.5 vs. 2.5 +/- 0.3 ml x 100 ml(-1) x min(-1), P < 0.05) and FVR was significantly lower (28.0 +/- 4.8 vs. 49.1 +/- 4.6 units, respectively, P < 0.05). These results indicate that increases in vascular resistance in the nonexercised limb induced by activation of the muscle chemoreflex can be attenuated by increases in calf volume.