Effects of aging and exercise training on spinotrapezius muscle microvascular PO2 dynamics and vasomotor control

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O(2) delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O(2) delivery to O(2) uptake, evidenced through improved microvascular Po(2) (Pm(O(2))), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ～6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify Pm(O(2)) in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline Pm(O(2)) (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting Pm(O(2)) and the time-delay before Pm(O(2)) fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the Pm(O(2)) in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.     

Exercise training and muscle microvascular oxygenation: functional role of nitric oxide

Exercise training induces multiple adaptations within skeletal muscle that may improve local O(2) delivery-utilization matching (i.e., Po(2)mv). We tested the hypothesis that increased nitric oxide (NO) function is intrinsic to improved muscle Po(2)mv kinetics from rest to contractions after exercise training. Healthy young Sprague-Dawley rats were assigned to sedentary (n = 18) or progressive treadmill exercise training (n = 10; 5 days/wk, 6-8 wk, final workload of 60 min/day at 35 m/min, -14% grade) groups. Po(2)mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP, NO donor; 300 μM), and N(G)-nitro-l-arginine methyl ester (l-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained rats had greater peak oxygen uptake (Vo(2peak)) than their sedentary counterparts (81 ± 1 vs. 72 ± 2 ml·kg(-1)·min(-1), respectively; P < 0.05). Exercise-trained rats had significantly slower Po(2)mv fall throughout contractions (τ(1); time constant for the first component) during control (sedentary: 8.1 ± 0.6; trained: 15.2 ± 2.8 s). Compared with control, SNP slowed τ(1) to a greater extent in sedentary rats (sedentary: 38.7 ± 5.6; trained: 26.8 ± 4.1 s; P > 0.05) whereas l-NAME abolished the differences in τ(1) between sedentary and trained rats (sedentary: 12.0 ± 1.7; trained: 11.2 ± 1.4 s; P < 0.05). Our results indicate that endurance exercise training leads to greater muscle microvascular oxygenation across the metabolic transient following the onset of contractions (i.e., slower Po(2)mv kinetics) partly via increased NO-mediated function, which likely constitutes an important mechanism for training-induced metabolic adaptations.     

Exercise training blunts microvascular rarefaction in the metabolic syndrome

Reduced skeletal muscle microvessel density (MVD) in the obese Zucker rat (OZR) model of the metabolic syndrome is a function of a chronic reduction in vascular nitric oxide (NO) bioavailability. Previous studies suggest that exercise can improve NO bioavailability and reduce chronic inflammation and that low vascular NO bioavailability may be associated with impaired angiogenic responses via increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. As such, we hypothesized that chronic exercise (EX) would increase NO bioavailability in OZR and blunt microvascular rarefaction through reduced MMP activity, and potentially via altered plasma cytokine levels. Ten weeks of treadmill exercise (1 h/day, 5 days/wk, 22 m/min) reduced body mass and fasting insulin and triglyceride levels in EX-OZR vs. sedentary (SED) OZR. In EX-OZR, gastrocnemius muscle MVD was improved by 19 +/- 4%, whereas skeletal muscle arteriolar dilation and conduit arterial methacholine-induced NO release were increased. In EX-OZR, functional hyperemia was improved vs. SED-OZR, and minimum vascular resistance within perfused gastrocnemius muscle was reduced, although no change in arteriolar stiffness was identified. Western blotting and gelatin zymography demonstrated that neither expression nor activity of MMP-2 or MMP-9 was altered in skeletal muscle of EX vs. SED animals. Plasma markers of inflammation associated with angiogenesis, monocyte chemoattractant protein-1 and IL-1beta, were increased in SED-OZR and were reduced with training, whereas IL-13 was reduced in SED-OZR and increased with exercise. These data suggest that exercise-induced improvements in skeletal muscle MVD in OZR are associated with increased NO bioavailability and may stem from altered inflammatory profiles rather than MMP function.     

Microvascular injury after ischemia and reperfusion in skeletal muscle of exercise-trained rats

Ischemia and reperfusion in skeletal muscle is associated with increases in total vascular resistance (Rt) and the microvascular permeability to plasma proteins. To determine whether exercise training can attenuate ischemia and reperfusion-induced microvascular injury in skeletal muscle, intact (with skin) and skinned, maximally vasodilated (papaverine), isolated hindquarters of control (C) and exercise-trained (ET) rats were subjected to ischemia (intact 120 min; skinned 60 min) followed by 60 min of reperfusion. ET rats ran on a motorized treadmill at 32 m/min (8% grade), 2 h/day for 12 wk, whereas the C rats were cage confined. Before ischemia, ET hindquarters had higher isogravimetric flow, lower Rt, and similar solvent drag reflection coefficients (sigma f) compared with C. During reperfusion in intact hindquarters, flow was higher (P less than 0.05) and Rt tended to be lower (15 +/- 2 vs. 25 +/- 5 mmHg.ml-1.min.100 g; P less than 0.1) in ET compared with C; however, in skinned hindquarters flow and Rt (14 +/- 2 vs. 13 +/- 2 mmHg.ml-1.min.100 g) were not different between C and ET. During reperfusion, sigma f was reduced (P less than 0.05) in both intact (C 0.68 +/- 0.03; ET 0.68 +/- 0.02) and skinned (C 0.66 +/- 0.03; ET 0.68 +/- 0.03) hindquarters, indicative of an increased microvascular permeability to plasma proteins. These results indicate that exercise training did not attenuate the microvascular injury (increased Rt and decreased sigma f) associated with ischemia and reperfusion in rat skeletal muscle.     

Upregulation of platelet (L)-arginine: nitric oxide pathway after exercise training in hypertension

We investigated whether physical exercise can affect platelet L-arginine?- nitric oxide pathway in spontaneously hypertensive rats (SHR). Sixteen male SHR and 16 Wistar Kyoto rats (WKY) were divided among exercise (EX) and sedentary (SED) groups. After 20?weeks of treadmill training, systolic blood pressure (mm?Hg) was significantly lower in exercised spontaneously hypertensive rats (SHR/EX; 138?± 8) than in sedentary spontaneously hypertensive rats (SHR/SED; 214?± 9). Exercise significantly increased platelet L-arginine transport (pmol L-arginine·(10(9) cells)(-1)·min(-1)), assessed by incubation with L-[(3)H]-arginine, in both WKY (SED, 0.196?± 0.054 compared with EX, 0.531?± 0.052) and SHR (SED, 0.346?± 0.076 compared with EX, 0.600?± 0.049). Nitric oxide synthase (NOS) activity (pmol L-citrulline·(10(8) cells)(-1)), measured by the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, was significantly increased in SHR/EX (0.072?± 0.007) compared with SHR/SED (0.038?± 0.007), but no changes were observed in WKY. The iNOS and eNOS protein levels assessed by Western blot were not affected by exercise. This upregulation of the platelet L-arginine-NO pathway may attenuate the risk of thromboembolic events, supporting the role of exercise in hypertension management.     

Exercise training prevents the inflammatory response to hypoxia in cremaster venules.

Systemic hypoxia produces microvascular inflammation in several tissues, including skeletal muscle. Exercise training (ET) has been shown to reduce the inflammatory component of several diseases. Alternatively, ET could influence hypoxia-induced inflammation by improving tissue oxygenation or increasing mechanical antiadhesive forces at the leukocyte-endothelial interface. The effect of 5 wk of treadmill ET on hypoxia-induced microvascular inflammation was studied in the cremaster microcirculation of rats using intravital microscopy. In untrained rats, hypoxia (arterial Po(2) = 32.3 +/- 2.1 Torr) increased leukocyte-endothelial adherence from 2.3 +/- 0.4 to 10.2 +/- 0.3 leukocytes per 100 microm of venule (P < 0.05) and was accompanied by extravasation of FITC-labeled albumin after 4 h of hypoxia (extra-/intravascular fluorescence intensity ratio = 0.50 +/- 0.07). These responses were attenuated in ET (leukocyte adherence was 1.5 +/- 0.4 during normoxia and 1.8 +/- 0.7 leukocytes per 100 mum venule after 10 min of hypoxia; extra-/intravascular fluorescence intensity ratio = 0.11 +/- 0.02; P < 0.05 vs. untrained) despite similar reductions of arterial (32.4 +/- 1.8 Torr) and microvascular Po(2) (measured with an oxyphor-quenching method) in both groups. Shear rate decreased during hypoxia to similar extents in ET and untrained rats. In addition, circulating blood leukocyte count was similar in ET and untrained rats. The effects of ET on hypoxia-induced leukocyte-endothelial adherence remained up to 4 wk after discontinuing training. Thus ET attenuated hypoxia-induced inflammation despite similar effects of hypoxia on tissue Po(2), venular shear rate, and circulating leukocyte count.     

The effects of aerobic exercise training on the age-related lipid peroxidation, Schwann cell apoptosis and ultrastructural changes in the sciatic nerve of rats

The potential role of exercise in preventing the age-related spontaneous peripheral neuropathy has not been studied. We examined the effects of long-term aerobic exercise training on lipid peroxidation, Schwann cell (SC) apoptosis and ultrastructural changes in the sciatic nerve of rats during aging. Three groups of 12-week old Wistar rats ran on a treadmill for 6, 9 and 12 months (exercise trained (ET) group, n=10 each) according to an exercise training program targeted at a speed of 22 m/min (at 7 degrees incline), 60 min/day, 6 days/week. Three corresponding groups of untrained rats were used as the controls (sedentary (SED) group). At the end of each period, sciatic nerve biopsies were performed, and processed for biochemical, immunohistochemical and ultrastructural analyses. The results showed that aging was associated with an increased level of nerve malondialdehyde (MDA, marker of lipid peroxidation) and a higher number of SC apoptosis in SED group. The SED group showed irregular nerve fibers with thin myelin sheaths and areas of myelin-axon detachment. However, the ET group had significantly diminished nerve lipid peroxidation and SC apoptosis. In the ET group, nerve fibers had a thick myelin sheath with frequent folding. These findings suggest that aerobic exercise training protects peripheral nerves by attenuating oxidative reactions, and preserving SCs and myelin sheath from pathologic changes, which occur during normal aging.     

Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium

Vascular oxidative stress contributes to endothelial dysfunction. Aerobic exercise training improves vascular function. The purpose of this study was to test the hypothesis that exercise training would improve the balance of antioxidant to prooxidant enzymes and reduce markers of oxidative stress in aortic endothelial cells (AEC). Female Yucatan miniature pigs either remained sedentary (SED) or were exercise trained (EX) for 16-19 wk. EX pigs had increased AEC SOD-1 protein levels and Cu/Zn SOD activity of the whole aorta compared with SED pigs. Protein levels of other antioxidant enzymes (SOD-2, catalase) were not affected by exercise training. Protein levels of p67(phox), a subunit of the prooxidant enzyme NAD(P)H oxidase, were reduced in EX vs. SED AEC. These EX adaptations were associated with lower AEC malondialdehyde levels and decreased phosphorylation of ERK-1/2. Endothelial nitric oxide synthase protein, protein nitrotyrosine content, and heme oxygenase-1 protein were not different in EX vs. SED pigs. We conclude that chronic aerobic exercise training influenced both antioxidant and prooxidant enzymes and decreased indexes of oxidative stress in AEC. These adaptations may contribute to improved endothelial function with exercise training.     

Exercise training reverses impaired skeletal muscle metabolism induced by artificial selection for low aerobic capacity

We have used a novel model of genetically imparted endurance exercise capacity and metabolic health to study the genetic and environmental contributions to skeletal muscle glucose and lipid metabolism. We hypothesized that metabolic abnormalities associated with low intrinsic running capacity would be ameliorated by exercise training. Selective breeding for 22 generations resulted in rat models with a fivefold difference in intrinsic aerobic capacity. Low (LCR)- and high (HCR)-capacity runners remained sedentary (SED) or underwent 6 wk of exercise training (EXT). Insulin-stimulated glucose transport, insulin signal transduction, and rates of palmitate oxidation were lower in LCR SED vs. HCR SED (P < 0.05). Decreases in glucose and lipid metabolism were associated with decreased β?-adrenergic receptor (β?-AR), and reduced expression of Nur77 target proteins that are critical regulators of muscle glucose and lipid metabolism [uncoupling protein-3 (UCP3), fatty acid transporter (FAT)/CD36; P < 0.01 and P < 0.05, respectively]. EXT reversed the impairments to glucose and lipid metabolism observed in the skeletal muscle of LCR, while increasing the expression of β?-AR, Nur77, GLUT4, UCP3, and FAT/CD36 (P < 0.05) in this tissue. However, no metabolic improvements were observed following exercise training in HCR. Our results demonstrate that metabolic impairments resulting from genetic factors (low intrinsic aerobic capacity) can be overcome by an environmental intervention (exercise training). Furthermore, we identify Nur77 as a potential mechanism for improved skeletal muscle metabolism in response to EXT.     

Age-dependent renal cortical microvascular loss in female mice

Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18-22 mo. Another comparable group was replenished with estrogen after Ovx (Ovx+E), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20-200 μm) was decreased in all aged groups compared with young controls (30.3 ± 5.8 vessels/mm2, P < 0.05), but tended to be lower in sham compared with Ovx and Ovx+E (9.9 ± 1.7 vs. 17.2 ± 4.2 and 18 ± 3.0 vessels/mm2, P = 0.08 and P = 0.02, respectively). Cortical density of larger microvessels (200-500 μm) decreased only in aged sham (P = 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in Ovx+E, in association with downregulated transforming growth factor-β signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen. However, estrogen may play a role in protecting the kidney by decreasing oxidative stress and attenuating mechanisms linked to renal interstitial fibrosis.     

Effects of aging and training status on ventilatory response during incremental cycling exercise

The aim of this study was to examine the effect of aging and training status on ventilatory response during incremental cycling exercise. Eight young (24 ± 5 years) and 8 older (64 ± 3 years) competitive cyclists together with 8 young (27 ± 4 years) and 8 older (63 ± 2 years) untrained individuals underwent a continuous incremental cycling test to exhaustion to determine ventilatory threshold (VT), respiratory compensation point (RCP), and maximal oxygen uptake (VO?max). In addition, the isocapnic buffering (IB) phase was calculated together with the hypocapnic hyperventilation. Ventilatory threshold occurred at similar relative exercise intensities in all groups, whereas RCP was recorded at higher intensities in young and older cyclists compared to the untrained subjects. The IB phase, reported as the difference between VT and RCP and expressed either in absolute (ml·min?1·kg?1 VO?) or in relative terms, was greater (p < 0.01) in both young and older trained cyclists than in untrained subjects, who were also characterized by a lower exercise capacity. Isocapnic buffering was particularly small in the older untrained volunteers. Although young untrained and older trained subjects had a similar level of VO?max, older athletes exhibited a larger IB. In addition, a higher absolute but similar relative IB was observed in young vs. older cyclists, despite a higher VO?max in the former. In conclusion, the present study shows that aging is associated with a reduction of the IB phase recorded during an incremental exercise test. Moreover, endurance training induces adaptations that result in an enlargement of the IB phase independent of age. This information can be used for the characterization and monitoring of the physiological adaptations induced by endurance training.     

Cardiac function following prolonged exercise: influence of age

This study sought to determine the influence of age on the left ventricular (LV) response to prolonged exercise (PE; 150 min). LV systolic and diastolic performance was assessed using echocardiography (ECHO) before (pre) and 60 min following (post) exercise performed at 80% maximal aerobic power in young (28 ± 4.5 years; n = 18; mean ± SD) and middle-aged (52 ± 3.9 years; n = 18) participants. LV performance was assessed using two-dimensional ECHO, including speckle-tracking imaging, to determine LV strain (LV S) and LV S rate (LV SR), in addition to Doppler measures of diastolic function. We observed a postexercise elevation in LV S (young: -19.5 ± 2.1% vs. -21.6 ± 2.1%; middle-aged: -19.9 ± 2.3% vs. -20.8 ± 2.1%; P < 0.05) and LV SR (young: -1.19 ± 0.1 vs. -1.37 ± 0.2; middle-aged: -1.20 ± 0.2 vs. -1.38 ± 0.2; P < 0.05) during recovery in both groups. Diastolic function was reduced during recovery, including the LV SR ratio of early-to-late atrial diastolic filling (SR(e/a)), in young (2.35 ± 0.7 vs. 1.89 ± 0.5; P < 0.01) and middle-aged (1.51 ± 0.5 vs. 1.05 ± 0.2; P < 0.01) participants, as were conventional indices including the E/A ratio. Dobutamine stress ECHO revealed a postexercise depression in LV S in response to increasing dobutamine dose, which was similar in both young (pre-exercise dobutamine 0 vs. 20 μg·kg(-1)·min(-1): -19.5 ± 2.1 vs. -27.2 ± 2.2%; postexercise dobutamine 0 vs. 20 μg·kg(-1)·min(-1): -21.6 ± 2.1 vs. -23.7 ± 2.2%; P < 0.05) and middle-aged participants (pre: -19.9 ± 2.3 vs. -25.3 ± 2.7%; post: -20.8 ± 2.1 vs. -23.5 ± 2.7; P < 0.05). This was despite higher noradrenaline concentrations immediately postexercise in the middle-aged participants compared with young (4.26 ± 2.7 nmol/L vs. 3.00 ± 1.4 nmol/L; P = 0.12). These data indicate that LV dysfunction is observed following PE and that advancing age does not increase the magnitude of this response.     

Resistance and aerobic exercise protects against acute endothelial impairment induced by a single exposure to hypertension during exertion

Resistance and aerobic exercise is recommended for cardiovascular health and disease prevention. However, the accompanying increase in arterial pressure during resistance exercise may be detrimental to vascular health. This study tests the vascular benefits of aerobic compared with resistance exercise on preventing impaired vascular function induced by a single weight lifting session that is associated with acute hypertension. Healthy, lean sedentary (SED) subjects, weight lifters, runners (>15 miles/wk), and cross trainers (chronic aerobic and resistance exercisers), underwent a single progressive leg press weight lifting session with blood pressure measurements. Brachial artery flow-mediated vasodilation (FMD; an index of arterial endothelial function) was determined using ultrasonography immediately before and after weight lifting. Sublingual nitroglycerin (0.4 mg) was used to determine endothelium-independent dilation after weight lifting. All subjects were normotensive with similar blood pressure responses during exercise. Baseline FMD was lower in runners (5.4 ± 0.5%; n = 13) and cross trainers (4.44 ± 0.3%; n = 13) vs. SED (8.5 ± 0.8%; n = 13; P = 0.037). Brachial FMD improved in conditioned weight lifters (to 8.8 ± 0.9%; P = 0.007) and runners (to 7.6 ± 0.6%; P < 0.001) but not cross trainers (to 5.3 ± 0.6%; P = NS) after acute hypertension. FMD was decreased in SED (to 5.7 ± 0.4%; P = 0.019). Dilation to nitroglycerin was similar among groups. These data suggest that endothelial responses are maintained after exposure to a single bout of weight lifting in resistance and aerobic athletes. Resistance and aerobic exercise may confer similar protection against acute vascular insults such as exertional hypertension.     

Sympathetic response to maximal bicycle exercise before and after leg strength training

Plasma catecholamine concentrations at rest and in response to maximal exercise on the cycle ergometer (278 +/- 15 watts, 6 min duration) have been measured on seven young active male subjects (19 +/- 1 years old; 80 +/- 3 kg; 176 +/- 3 cm) prior to and after a eight week leg strength training program (5RM, squat and leg press exercise). Strength training resulted in a significant increase in performance on squat (103 +/- 3 to 140 +/- 5 kg) and leg press exercise (180 +/- 9 to 247 +/- 15 kg) associated with a small significant increase in lean body mass (64.5 +/- 2.2 to 66.3 +/- 2.1 kg) and no change in maximal oxygen consumption (47.5 +/- 1.3 to 46.9 +/- 1.2 ml X kg-1 X min-1). Plasma norepinephrine (NE) and epinephrine (E) concentrations (pg X mL-1) were not significantly different before and after training at rest (NE: 172 +/- 19 vs 187 +/- 30; E: 33 +/- 10 vs 76 +/- 16) or in response to maximal exercise (NE: 3976 +/- 660 vs 4163 +/- 1081; E: 1072 +/- 322 vs 1321 +/- 508). Plasma lactate concentrations during recovery were similar before and after training (147 +/- 5 vs 147 +/- 15 mg X dL-1). Under the assumption that the "central command" is reduced for a given absolute workload on the bicycle ergometer following leg strength training, these observations support the hypothesis that the sympathetic response to exercise is under the control of information from muscle chemoreceptors.     

Progressive resistance training without volume increases does not alter arterial stiffness and aortic wave reflection

Endurance exercise is efficacious in reducing arterial stiffness. However, the effect of resistance training (RT) on arterial stiffening is controversial. High-intensity, high-volume RT has been shown to increase arterial stiffness in young adults. We tested the hypothesis that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume would not elicit increases in either central or peripheral arterial stiffness or alter aortic pressure wave reflection in young men and women. The RT group (n = 24; 21 +/- 1 years) performed two sets of 8-12 repetitions to volitional fatigue on seven exercise machines on 3 days/week for 12 weeks, whereas the control group (n = 18; 22 +/- 1 years) did not perform RT. Central and peripheral arterial pulse wave velocity (PWV), aortic pressure wave reflection (augmentation index; AIx), brachial flow-mediated dilation (FMD), and plasma levels of nitrate/nitrite (NOx) and norepinephrine (NE) were measured before and after RT. RT increased the one-repetition maximum for the chest press and the leg extension (P < 0.001). RT also increased lean body mass (P < 0.01) and reduced body fat (%; P < 0.01). However, RT did not affect carotid-radial, carotid-femoral, and femoral-distal PWV (8.4 +/- 0.2 vs. 8.0 +/- 0.2 m/sec; 6.5 +/- 0.1 vs. 6.3 +/- 0.2 m/sec; 9.5 +/- 0.3 vs. 9.5 +/- 0.3 m/sec, respectively) or AIx (2.5% +/- 2.3% vs. 4.8% +/- 1.8 %, respectively). Additionally, no changes were observed in brachial FMD, NOx, NE, or blood pressures. These results suggest that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume does not increase central or peripheral arterial stiffness or alter aortic pressure wave characteristics in young subjects.     

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.     

Moderate exercise training provides left ventricular tolerance to acute pressure overload

The present study evaluated the impact of moderate exercise training on the cardiac tolerance to acute pressure overload. Male Wistar rats were randomly submitted to exercise training or sedentary lifestyle for 14 wk. At the end of this period, the animals were anaesthetized, mechanically ventilated, and submitted to hemodynamic evaluation with biventricular tip pressure manometers. Acute pressure overload was induced by banding the descending aorta to induce a 60% increase of peak systolic left ventricular pressure during 120 min. This resulted in the following experimental groups: 1) sedentary without banding (SED + Sham), 2) sedentary with banding (SED + Band), and 3) exercise trained with banding (EX + Band). In response to aortic banding, SED + Band animals could not sustain the 60% increase of peak systolic pressure for 120 min, even with additional narrowing of the banding. This was accompanied by a reduction of dP/dt(max) and dP/dt(min) and a prolongation of the time constant tau, indicating impaired systolic and diastolic function. This impairment was not observed in EX + Band (P < 0.05 vs. SED + Band). Additionally, compared with SED + Band, EX + Band presented less myocardial damage, exhibited attenuated protein expression of active caspase-3 and NF-κB (P < 0.016), and showed less protein carbonylation and nitration (P < 0.05). These findings support our hypothesis that exercise training has a protective role in the modulation of the early cardiac response to pressure overload.     

Carnitine supplementation effects on nonenzymatic antioxidants in young rats submitted to exhaustive exercise stress

Previous studies have demonstrated that exercise stress increases oxidative stress in rats. However, antioxidant supplement therapy effects on reactive oxygen substances are conflicting. We evaluated the effects of carnitine on renal nonenzymatic antioxidants in young rats submitted to exhaustive exercise stress. Wistar rats were divided into 3 groups: (a) control group (not submitted to exercise stress), (b) exercise stress group, and (c) exercise stress and carnitine group. The rats from group 3 were treated with gavage administration of 1 ml of carnitine (5 mg·kg?1) for 7 consecutive days. The animals from groups 2 and 3 were submitted to a bout of swimming exhaustive exercise stress. Kidney samples were analyzed for reactive substances to thiobarbituric acid by malondialdehyde (MDA), reduced glutathione (GSH), and vitamin-E levels. Carnitine treatment attenuated MDA increase caused by exercise stress (1: 0.16 ± 0.02 vs. 2: 0.34 ± 0.07 vs. 3: 0.1 ± 0.01 mmmol per milligram of protein; p < 0.0001). It also increased the renal levels of GSH (1: 23 ± 4 vs. 2: 23 ± 2 vs. 3: 58 ± 9 μmol per gram of protein; p < 0.0001); however, it did not change renal vitamin E (1: 24 ± 5 vs. 2: 27 ± 1 vs. 3: 28 ± 5 μM per gram of tissue; p < 0.001). In conclusion, carnitine improved oxidative stress and partially improved the nonenzymatic antioxidant activity in young rats submitted to exhaustive exercise stress.     

Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age

Long-term or untreated diabetes leads to micro- and macrovascular complications. However, there are few tests to evaluate microvascular function. A postcontraction blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) technique was exploited to measure peripheral microvascular function in diabetics and healthy controls matched with respect to age, body mass index, and physical activity. Postcontraction BOLD microvascular response was measured following 1-s maximal isometric ankle dorsiflexion in individuals with diabetes mellitus type I [DMI, n = 15, age 33 ± 3 yr (means ± SE), median diabetes duration = 5.5 yr] and type II (DMII, n = 16, age 45 ± 2 yr, median duration = 2.4 yr); responses were compared with controls (CONI and CONII). Peripheral macrovascular function of the popliteal and tibial arteries was assessed during exercise hyperemia with phase contrast magnetic resonance angiography following repetitive exercise. There were no group differences as a result of diabetes in peripheral microvascular function (peak BOLD response: DMI = 2.04 ± 0.38% vs. CONI = 2.08 ± 0.48%; DMII = 0.93 ± 0.24% vs. CONII = 1.13 ± 0.24%; mean ± SE), but the BOLD response was significantly influenced by age (partial r = -0.384, P = 0.003), supporting its sensitivity as a measure of microvascular function. Eleven individuals had no microvascular BOLD response, including three diabetics with neuropathy and four controls with a family history of diabetes. There were no differences in peripheral macrovascular function between groups when assessing exercise hyperemia or the pulsitility and resistive indexes. Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health.     

Pulmonary ventilation, blood gases, and blood pH after training of the arms or the legs.

In two groups of young healthy subjects who performed arm training (N = 5) and leg training (N = 5), respectively, the respiratory adaptation to submaximal exercise with trained and nontrained muscle groups was compared by measurement of the ventilatory equivalent (Ve/Vo2, pH, and blood gases (Pco2, Po2, and So2) in arterial blood and in venous blood from exercising extremities. After training Ve/Vo2 was significantly reduced during exercise with trained muscles, but unchanged during exercise with nontrained muscles. The reduction in Ve/Vo2 was closely related to a less pronounced increase in heart rate and in arterial lactate content, but showed no quantitative correlation to changes in arterial adaptations in trained muscles are mainly responsible for the reduction in Ve/Vo2. After training during exercise with trained as well as nontrained muscles a shift to the right of the blood oxygen dissociation curve occurred as extremities was lower while corresponding Po2 was higher.