Treadmill Exercise In Rats Research Articles

Systemic and tissue-specific spexin response to acute treadmill exercise in rats

Spexin (SPX) is a 14-amino-acid peptide that plays an important role in the regulation of metabolism and energy homeostasis. It is well known that a variety of bioactive molecules released into the circulation by organs and tissues in response to acute and chronic exercise, known as exerkines, mediate the benefits of exercise by improving metabolic health. However, it is unclear whether acute exercise affects SPX levels in the circulation and peripheral tissues. This study aimed to determine whether acute treadmill exercise induces plasma SPX levels, as well as mRNA expression and immunostaining of SPX in skeletal muscle, adipose tissue, and liver. Male Sprague Dawley rats were divided into sedentary and acute exercise groups. Plasma, soleus (SOL), extensor digitorum longus (EDL), adipose tissue, and liver samples were collected at six time points (0, 1, 3, 6, 12, and 24 h) following 60 min of acute treadmill exercise at a speed of 25 m/min and 0 % grade. Acute exercise increased plasma SPX levels and induced mRNA expression of Spx in the SOL, EDL, and liver. Immunohistochemical analysis demonstrated that acute exercise led to a decrease in SPX immunostaining in the liver. Taken together, these findings suggest that SPX increases in response to acute exercise as a potential exerkine candidate, and the liver may be one of the sources of acute exercise-induced plasma SPX levels in rats. However, a comprehensive analysis is needed to fully elucidate the systemic response of SPX to acute exercise, as well as the tissue from which SPX is secreted.

Time-course and muscle-specific gene expression of matrix metalloproteinases and inflammatory cytokines in response to acute treadmill exercise in rats.

The extracellular matrix (ECM) of skeletal muscle plays a pivotal role in tissue repair and growth, and its remodeling tightly regulated by matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and inflammatory cytokines. This study aimed to investigate changes in the mRNA expression of MMPs (Mmp-2 and Mmp-14), TIMPs (Timp-1 and Timp-2), and inflammatory cytokines (Il-1β, Tnf-α, and Tgfβ1) in the soleus (SOL) and extensor digitorum longus (EDL) muscles of rats following acute treadmill exercise. Additionally, muscle morphology was examined using hematoxylin and eosin (H&E) staining. Male rats were subjected to acute treadmill exercise at 25m/min for 60min with a %0 slope. The mRNA expression of ECM components and muscle morphology in the SOL and EDL were assessed in both sedentary and exercise groups at various time points (immediately (0) and 1, 3, 6, 12, and 24h post-exercise). Our results revealed a muscle-specific response, with early upregulation of the mRNA expression of Mmp-2, Mmp-14, Timp-1, Timp-2, Il-1β, and Tnf-α observed in the SOL compared to the EDL. A decrease in Tgfβ1 mRNA expression was evident in the SOL at all post-exercise time points. Conversely, Tgfβ1 mRNA expression increased at 0 and 3h post-exercise in the EDL. Histological analysis also revealed earlier cell infiltration in the SOL than in the EDL following acute exercise. Our results highlight how acute exercise modulates ECM components and muscle structure differently in the SOL and EDL muscles, leading to distinct muscle-specific responses.

Sex differences in the purinergic 2 receptor-mediated blood pressure response to treadmill exercise in rats with simulated peripheral artery disease.

We investigated the role played by ATP-sensitive purinergic 2 (P2) receptors in evoking the pressor response to treadmill exercise in male and female rats with and without femoral arteries that were ligated for ∼72 h to induce simulated peripheral artery disease (PAD). We hypothesized that PPADS (P2 receptor antagonist, 10 mg iv) would reduce the pressor response to 4 min of treadmill exercise (15 m·min-1, 1° incline) and steady-state exercise plasma norepinephrine (NE) values in male and female rats, and that the magnitude of effect of PPADS would be greater in rats with simulated PAD ("ligated") than in sham-operated rats. In males, PPADS significantly reduced the difference between steady-state exercise and baseline mean arterial pressure (ΔMAP) response to treadmill exercise in sham (n = 8; pre-PPADS: 12 ± 2, post-PPADS: 1 ± 5 mmHg; P = 0.037) and ligated (n = 4; pre-PPADS: 20 ± 2, post-PPADS: 11 ± 3 mmHg; P = 0.028) rats with a similar magnitude of effect observed between groups (P = 0.720). In females, PPADS had no effect on the ΔMAP response to treadmill exercise in sham (n = 6; pre-PPADS: 9 ± 2, post-PPADS: 7 ± 2 mmHg; P = 0.448) or ligated (n = 6; pre-PPADS: 15 ± 2, post-PPADS: 16 ± 3 mmHg; P = 0.684) rats. When NE values were grouped by sex independent of ligation/sham status, PPADS significantly reduced plasma NE in male (P = 0.016) and female (P = 0.027) rats. The data indicate that P2 receptors contribute to the sympathetic response to exercise in both male and female rats but that the sympathoexcitatory role for P2 receptors translates into an obligatory role in the blood pressure response to exercise in male but not in female rats.NEW & NOTEWORTHY Here, we demonstrate that purinergic 2 (P2) receptors contribute significantly to the blood pressure response to treadmill exercise in male rats both with and without simulated PAD induced by femoral artery ligation. We found no role for P2 receptors in the blood pressure response to treadmill exercise in female rats, thus revealing clear sex differences in P2 receptor-mediated blood pressure control during exercise.

Functional connectivity in central nucleus of amygdala, paraventricular hypothalamus, and nucleus tractus solitarii circuits during high-intensity endurance treadmill exercise in rats

High-intensity endurance exercise (HIE) induces negative emotions alongside fatigue, suffering, and changes in cardiovascular responses, and these regulations could be important for athletic performance. Previous studies have reported that limbic and brain stem regions, including the central nucleus of the amygdala (CeA), the paraventricular nucleus of the hypothalamus (PVH), and the nucleus tractus solitarii (NTS), play important roles in emotional response and autonomic cardiovascular regulation. However, how these brain regions interact during HIE remains unclear. In this study, Wistar rats were subjected to 90-min treadmill running sessions at different endurance exercise intensities (sedentary, low-intensity, and high-intensity: 0, 20, and 34 m/min, respectively; n = 9 per group). After exercise, brain tissues were extracted and examined for c-Fos immediate early gene expression in brain regions such as the CeA, PVH, and NTS at each exercise intensity. The c-Fos-positive cells were counted, and then a partial correlation analysis was performed to examine the functional connectivity during exercise. As a result, the numbers of c-Fos-positive cells in the CeA, PVH, and NTS increased in an exercise intensity-dependent manner. Furthermore, partial correlation analyses of c-Fos-positive cells between CeA and NTS (CeA-NTS), PVH and NTS (PVH-NTS), and CeA and PVH (CeA-PVH) exhibited significant correlation coefficients during HIE but not during sedentary and low-intensity endurance exercises. Thus, these results suggest that functional connectivity between CeA-PVH, PVH-NTS, and CeA-NTS may be enhanced during HIE. This enhanced functional connectivity may also be involved in emotional and cardiovascular regulation during exercise.

Evaluation of jacketed telemetry in rats for cardiorespiratory phenotyping at exercise

The challenge of cardiorespiratory function through physical exercise is highly relevant to reveal pathological phenotypes, both in humans and animals, but available monitoring tools (implanted telemetry, metabolic chamber) remain challenging to use in the context of exercise. Recently, jacketed telemetry systems for small laboratory animals have been developed, allowing non-invasive physiological monitoring in various conditions. The aim of this work was to evaluate the feasibility, using this new technology, to monitor cardiorespiratory function during treadmill exercise in rats. The effects of a moderate-intensity treadmill exercise protocol were monitored using a non-invasive telemetric jacket on a group of untrained male wistar rats (N = 9, 9–10 weeks). This incremental protocol consisted in increase the speed level of 5 cm/sec every 2 minutes (Speed: from 10 to 35 cm/sec max). Heart rate (HR), respiratory rate (RespR) and activity level (AL) were monitored with a small electronic Bluetooth device (15 g) and analyzed during a control state (Baseline), the last 30 seconds of each speed level and at post-exercise recovery. The animals were equipped with the device and placed back in their home cage. After 25 minutes of stabilization, HR was 392 ± 36 bpm, RespR was 173 ± 53 brpm, and AL was 15 ± 12 mg. All animals successfully ran on the treadmill with the jacket to the maximum speed of 35 cm/sec. Exercise induced a significant physiological increase in HR (+26%, 104 ± 21 bpm, P < 0.01) and RespR (+73%, 126 ± 22 brpm, P < 0.01). In conclusion, this novel telemetry jacket can be used to monitor cardiorespiratory parameters adaptation during a standard forced exercise protocol. Jacketed telemetry provides a completely non-invasive way to study the phenotypes of animals avoiding any additional risk on fragile pathological models and meeting the regulatory 3Rs requirements. As illustrated phenotype characterization can be enriched with a monitoring of the animal in various situations (treadmill, home cage, but also metabolic or hypoxia cage, etc.…).

Exercise Modulates Brain Glucose Utilization Response to Acute Cocaine.

Exercise, a proven method of boosting health and wellness, is thought to act as a protective factor against many neurological and psychological diseases. Recent studies on exercise and drug exposure have pinpointed some of the neurological mechanisms that may characterize this protective factor. Using positron emission tomography (PET) imaging techniques and the glucose analog [18F]-Fluorodeoxyglucose (18F-FDG), our team sought to identify how chronic aerobic exercise modulates brain glucose metabolism (BGluM) after drug-naïve rats were exposed to an acute dose of cocaine. Using sedentary rats as a control group, we observed significant differences in regional BGluM. Chronic treadmill exercise treatment coupled with acute cocaine exposure induced responses in BGluM activity in the following brain regions: postsubiculum (Post), parasubiculum (PaS), granular and dysgranular insular cortex (GI and DI, respectively), substantia nigra reticular (SNR) and compact part dorsal tier (SNCD), temporal association cortex (TeA), entopenduncular nucleus (EP), and crus 1 of the ansiform lobule (crus 1). Inhibition, characterized by decreased responses due to our exercise, was found in the ventral endopiriform nucleus (VEn). These areas are associated with memory and various motor functions. They also include and share connections with densely dopaminergic areas of the mesolimbic system. In conclusion, these findings suggest that treadmill exercise in rats mediates brain glucose response to an acute dose of cocaine differently as compared to sedentary rats. The modulated brain glucose utilization occurs in brain regions responsible for memory and association, spatial navigation, and motor control as well as corticomesolimbic regions related to reward, emotion, and movement.

Early Signs of Bone and Cartilage Changes Induced by Treadmill Exercise in Rats.

This study aims to investigate the earliest alterations of bone and cartilage tissues as a result of different exercise protocols in the knee joint of Wistar rats. We hypothesize that pretraining to a continuous intense running protocol would protect the animals from cartilage degeneration. Three groups of animals were used: (i) an adaptive (pretraining) running group that ran for 8 weeks with gradually increasing velocity and time of running followed by a constant running program (6 weeks of 1.12 km/hour running per day); (ii) a non-adaptive running (constant running) group that initially rested for 8 weeks followed by 6 weeks of constant running; and (iii) a non-running (control) group. At weeks 8, 14, and 20 bone and cartilage were analyzed. Both running groups developed mild symptoms of cartilage irregularities, such as chondrocyte hypertrophy and cell clustering in different cartilage zones, in particular after the adaptive running protocol. As a result of physical training in the adaptive running exercise a dynamic response of bone was detected at week 8, where bone growth was enhanced. Conversely, the thickness of epiphyseal trabecular and subchondral bone (at week 14) was reduced due to the constant running in the period between 8 and 14 weeks. Finally, the intermediate differences between the two running groups disappeared after both groups had a resting period (from 14 to 20 weeks). The adaptive running group showed an increase in aggrecan gene expression and reduction of MMP2 expression after the initial 8 weeks running. Thus, the running exercise models in this study showed mild bone and cartilage/chondrocyte alterations that can be considered as early-stage osteoarthritis. The pretraining adaptive protocol before constant intense running did not protect from mild cartilage degeneration. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Even Small Changes in Body Temperature Can Affect the Cardiac Function in Anesthetized Mice

Heart rate (HR) increases at the beginning of dynamic exercise, then remains constant or gradually increases in response to the exercise intensity. Both central command and the exercise pressor reflex (EPR) are thought to play an important role for this tachycardic response. Recently, the contribution of transient receptor potential vanilloid 1 (TRPV1) channel to the EPR has been reported (Smith SA et al, J Physiol 2010). However, the role of the TRPV1 channel on the exercise tachycardia during dynamic exercise remains largely unknown. We therefore examined the effect of systemic TRPV1 channel blockade or activation on the HR response to treadmill exercise in rats. Male Wistar rats were previously implanted with telemetry transmitters (TRM54P, Millar) to measure HR and arterial blood pressure (AP), and were trained to run on a treadmill. Both HR and mean AP (MAP) responses to treadmill running (20 or 40 m/min, 60 s) were compared before and after administration of TRPV1 channel agonists or antagonists. Sciatic nerve‐selective desensitization of TRPV1 channel by resiniferatoxin (10 µg, under anesthesia) significantly attenuated the HR response to exercise. Systemic administration of potent TRPV1 channel antagonist iodoresiniferatoxin (0.3 mg/kg ip), which has a partial agonist‐like effect, also attenuated it. On the other hand, either the TRPV1‐selective (SB366791; 3 mg/kg) or a nonselective (ruthenium red; 5 mg/kg) antagonists did not affect the HR response to exercise. In conclusion, desensitization of the TRPV1 channel‐expressing neurons attenuated the EPR‐mediated HR response during dynamic exercise in rats, suggesting that TRPV1‐expressing neurons play an important role for the HR response during dynamic exercise.

Circulating Levels of Key Myokines and Cytokines Immediately After Treadmill Exercise in Rats Fed Low‐fat or High‐fat Diets

A single bout of exercise (EX) can have benefits on glucose metabolism in both normal and insulin-resistant individuals. Several plasma proteins secreted by muscle and other tissues have been demonstrated to have roles in regulating energy metabolism including irisin, brain-derived neurotrophic factor (BDNF), and fibroblast growth factor-21 (FGF-21). However the effect on circulating levels of these proteins, after an acute bout of exercise in a model of dietary-induced insulin resistance is not known. Rats (male Sprague-Dawley, ~9-mos old) were fed standard low-fat diet (LFD), or a high-fat diet (60% of calories from fat; HFD) for 2 weeks. There were 4 groups of rats: 1) LFD-sedentary (LFD-SED), 2) HFD-SED, 3) LFD-EX, or 4) HFD-EX. On the day of the terminal experiment, rats in the EX groups ran for 30min on a treadmill at 18m/min. Immediately after the exercise bout, blood and tissue was taken from both EX and SED rats. HFD rats weighed more and had higher levels of insulin than LFD rats after 2 weeks o...

The Role of TRPV1‐Expressing Neurons in the Control of Heart Rate During Dynamic Exercise in Rats

Heart rate (HR) increases at the beginning of dynamic exercise, then remains constant or gradually increases in response to the exercise intensity. Both central command and the exercise pressor reflex (EPR) are thought to play an important role for this tachycardic response. Recently, the contribution of transient receptor potential vanilloid 1 (TRPV1) channel to the EPR has been reported (Smith SA et al, J Physiol 2010). However, the role of the TRPV1 channel on the exercise tachycardia during dynamic exercise remains largely unknown. We therefore examined the effect of systemic TRPV1 channel blockade or activation on the HR response to treadmill exercise in rats. Male Wistar rats were previously implanted with telemetry transmitters (TRM54P, Millar) to measure HR and arterial blood pressure (AP), and trained to run on a treadmill. Both HR and mean AP (MAP) responses to treadmill running (20 or 40 m/min, 60 s) were compared before and after administration of TRPV1 channel agonists or antagonists. Neither the TRPV1‐selective (SB366791; 3 mg/kg) nor the nonselective (ruthenium red; 5 mg/kg) antagonists affected the HR response to exercise. However, another TRPV1 selective antagonist 5′‐iodoresiniferatoxin (IRTX; 0.3 mg/kg) or a TRPV1 agonist capsaicin (20 mg/kg, sc under anesthesia) markedly attenuated the HR response to exercise. MAP responses to exercise were not affected by these drugs. Given the partial agonist‐like effect of IRTX, systemic desensitization of the TRPV1 channel‐expressing neurons attenuated the EPR‐mediated HR response during dynamic exercise in rats. In conclusion, TRPV1‐expressing neurons play an important role for the HR response during dynamic exercise.

Transient activation of mTOR following forced treadmill exercise in rats

The beneficial effect of exercise on hippocampal plasticity is possibly mediated by increased angiogenesis and neurogenesis. In angiogenesis, insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1, alpha subunit (HIF1α) are important factors, while the induction of neurogenesis requires signaling through the VEGF receptor, Flk-1 (VEGFR-2). VEGF expression is believed to be regulated by two distinct mTOR (mammalian target of Rapamycin)-containing multiprotein complexes mTORC1 and mTORC2, respectively. This study was initiated to investigate the effect of exercise on the expression of VEGF, cognate receptors, HIF1α, mTORC1, and mTORC2 in hippocampus and frontal cortex. To this end, we measured messenger RNA (mRNA) levels in rat brain using quantitative real-time polymerase chain reaction (real-time qPCR) after forced treadmill exercise for 1 day, 2 weeks, and 8 weeks. Rats were euthanized either immediately (0 h) or 24 h after last exercise session. Here, we show that exercise affected mRNA levels of VEGF, VEGFR2, and the coreceptor neuropilin 2 (NRP2) when the rats were euthanized immediately, whereas at 24 h only the expression of mTOR was regulated after a single bout of exercise. In conclusion, the effect of treadmill exercise on the VEGF system is acute rather than chronic and there is a transient activation of mTOR. More studies are needed to understand whether this could be beneficial in the treatment of neuropsychiatric disorders.

Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin resistance in the cerebellum

Although exercise usually improves motor performance, the underlying cellular changes in the cerebellum remain to be elucidated. This study aimed to investigate whether and how chronic treadmill exercise in young rats induced Purkinje cell changes to improve motor performance and rendered the cerebellum less vulnerable to toxin insults. After 1-wk familiarization of treadmill running, 6-wk-old male Wistar rats were divided into exercise and sedentary groups. The exercise group was then subjected to 8 wk of exercise training at moderate intensity. The rotarod test was carried out to evaluate motor performance. Purkinje cells in cerebellar slices were visualized by lucifer yellow labeling in single neurons and by calbindin immunostaining in groups of neurons. Compared with sedentary control rats, exercised rats not only performed better in the rotarod task, but also showed finer Purkinje cell structure (higher dendritic volume and spine density with the same dendritic field). The exercise-improved cerebellar functions were further evaluated by monitoring the long-lasting effects of intraventricular application of OX7-saporin. In the sedentary group, OX7-saporin treatment retarded the rotarod performance and induced ∼60% Purkinje cell loss in 3 wk. As a comparison, the exercise group showed much milder injuries in the cerebellum by the same toxin treatment. In conclusion, exercise training in young rats increased the dendritic density of Purkinje cells, which might play an important role in improving the motor performance. Furthermore, as Purkinje cells in the exercise group were relatively toxin resistant, the exercised rats showed good motor performance, even under toxin-treated conditions.

Dynamic arterial baroreflex function during high intensity exercise in humans: insights into sympathetic control

Dynamic arterial baroreflex function during high intensity exercise in humans: insights into sympathetic control

Acute shifts of baroreflex control of renal sympathetic nerve activity induced by treadmill exercise in rats

The present study aimed to investigate whether there was a resetting of the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) during exercise. Wistar female rats (n = 11) were chronically implanted with catheters for the measurement of systemic arterial (Pa) and central venous pressures and with electrodes for measurement of RSNA and electrocardiogram (ECG) at least 3 days before study. The baroreflex curve for RSNA was determined by changing Pa using rapid intravenous infusions of phenylephrine and nitroprusside. The baroreflex response curves for RSNA and HR were characterized by an inverse sigmoid function curve from which the response range, gain, centering point and minimum response were estimated. Exercise shifted the Pa-RSNA baroreflex curve upward and to the right and was associated with increases in response range of 122 +/- 44 % (P < 0.05), maximum response of 173 +/- 40 % (P < 0.05), maximum gain of 149 +/- 66 % (P < 0.05) and midpoint pressure of 15 +/- 5 mmHg (P < 0.05) compared with the pre-exercise level. After cessation of exercise, the Pa-RSNA baroreflex curve was suppressed vertically with a significant decrease in maximum response of 57 +/- 14 % (P < 0.05) compared with the pre-exercise level. These data suggest that the right-upward shift of baroreflex control of sympathetic nerve activity may play a critical role in raising and stabilizing Pa during exercise. The suppression of the baroreflex control of sympathetic nerve activity may partly explain the post-exercise inhibition of sympathetic nerve activity and contribute to the post-exercise hypotension.

Acute shifts of baroreflex control of renal sympathetic nerve activity induced by treadmill exercise in rats

The present study aimed to investigate whether there was a resetting of the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) during exercise. Wistar female rats (n = 11) were chronically implanted with catheters for the measurement of systemic arterial (Pa) and central venous pressures and with electrodes for measurement of RSNA and electrocardiogram (ECG) at least 3 days before study. The baroreflex curve for RSNA was determined by changing Pa using rapid intravenous infusions of phenylephrine and nitroprusside. The baroreflex response curves for RSNA and HR were characterized by an inverse sigmoid function curve from which the response range, gain, centering point and minimum response were estimated. Exercise shifted the Pa-RSNA baroreflex curve upward and to the right and was associated with increases in response range of 122 +/- 44 % (P < 0.05), maximum response of 173 +/- 40 % (P < 0.05), maximum gain of 149 +/- 66 % (P < 0.05) and midpoint pressure of 15 +/- 5 mmHg (P < 0.05) compared with the pre-exercise level. After cessation of exercise, the Pa-RSNA baroreflex curve was suppressed vertically with a significant decrease in maximum response of 57 +/- 14 % (P < 0.05) compared with the pre-exercise level. These data suggest that the right-upward shift of baroreflex control of sympathetic nerve activity may play a critical role in raising and stabilizing Pa during exercise. The suppression of the baroreflex control of sympathetic nerve activity may partly explain the post-exercise inhibition of sympathetic nerve activity and contribute to the post-exercise hypotension.

Method for Continuous Measurements of Renal Sympathetic Nerve Activity and Cardiovascular Function During Exercise in Rats

The sympathetic nervous system is believed to play a major role in regulating cardiovascular function during exercise. However, only a few direct measurements of sympathetic nervous activity during whole body dynamic exercise have been attempted. In the present study, we have established a method to allow routine measurement of renal sympathetic nerve activity (RSNA) and cardiovascular function during treadmill exercise in rats. We trained Wistar rats to run on the treadmill for a week before the surgery. At least 2 days before the experiment, electrodes for recording RSNA, electrocardiogram and electromyogram, and catheters for the measurements of systemic arterial and central venous pressures were implanted under aseptic conditions. Satisfactory signal to noise ratios were obtained in 80 %, 60 % and 40 % of the group at 1-3 days, 4-7 days and 8-10 days after the surgery, respectively. RSNA was successfully recorded without contamination by external noise during treadmill exercise. Treadmill exercise resulted in an abrupt increase in RSNA, by 82 % at 0.5 min, and then reached a stable level of ~40 % during the period of 5-30 min after the onset of treadmill exercise. This experimental model allows us to study the neural mechanisms involved in the regulation of cardiovascular function during dynamic exercise in rats.

Effects of nitric oxide synthase inhibition on vascular conductance during high speed treadmill exercise in rats.

To determine the functional role of nitric oxide (NO) in regulating vascular conductance during high intensity dynamic exercise in skeletal muscles composed of all major fibre types, female Wistar rats (277 +/- 4 g; n = 7) were run on a motor-driven treadmill at a speed and gradient (60 m min(-1), 10 % gradient) established to yield maximal oxygen uptake (V(O2,max)). Vascular conductance (ml min(-1) (100 g)(-1) mmHg(-1)), defined as blood flow normalised to mean arterial pressure (MAP), was determined using radiolabelled microspheres during exercise before and after NO synthase (NOS) inhibition with N (G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1), I.A.). The administration of L-NAME increased MAP from pre-L-NAME baseline values, demonstrating that NOS activity is reduced. The administration of L-NAME also reduced vascular conductance in 20 of the 28 individual hindlimb muscles or muscle parts examined during high speed treadmill exercise. These reductions in vascular conductance correlated linearly with the estimated sum of the percentage of slow twitch oxidative (SO) and fast twitch oxidative glycolytic (FOG) types of fibres in each muscle (Deltaconductance = -0.0082(%SO + %FOG) - 0.0105; r = 0.66; P < 0.001). However, if the reduction in vascular conductance found in the individual hindquarter muscles or muscle parts was expressed as a percentage decrease from the pre-L-NAME value (%Delta = (pre-L-NAME conductance - post-L-NAME conductance)/ pre-L-NAME conductance x 100), then the reduction in vascular conductance was similar in all muscles examined (average %Delta = -23 +/- 2 %). These results suggest that NO contributes substantially to the regulation of vascular conductance within and among muscles of the rat hindquarter during high intensity exercise. When expressed in absolute terms, the results suggest that the contribution of NO to the regulation of vascular conductance during high intensity exercise is greater in muscles that possess a high oxidative capacity. In contrast, if results are expressed in relative terms, then the contribution of NO to the regulation of vascular conductance during high intensity exercise is similar across the different locomotor muscles located in the rat hindlimb and independent of the fibre type composition.

Pre-exercise branched-chain amino acid administration increases endurance performance in rats.

This study investigated the effects of pre-exercise branched-chain amino acid (BCAA) administration on blood ammonia levels and on time to exhaustion during treadmill exercise in rats. Adult female Wistar rats were trained on a motor driven treadmill. After a 24-h fast, rats were injected intraperitoneally (i.p.) with 1 mL of placebo or BCAA (30 mg), 5 min before performing 30 min of submaximal exercise (N = 18) or running to exhaustion (N = 12). In both cases, rats were sacrificed immediately following exercise, and blood was collected for the measurement of glucose, nonesterified fatty acid (NEFA), lactic acid, BCAA, ammonia, and free-tryptophan (free-TRP) levels. Control values were obtained from sedentary rats that were subjected to identical treatments and procedures (N = 30). Plasma BCAA levels increased threefold within 5 min after BCAA administration. Mean run time to exhaustion was significantly longer (P < 0.01) after BCAA administration (99 +/- 9 min) compared with placebo (76 +/- 4 min). During exercise, blood ammonia levels were significantly higher (P < 0.01) in the BCAA treated compared with those in the placebo treated rats both in the 30-min exercise bout (113 +/- 25 mumol.L-1 (BCAA) vs 89 +/- 16 mumol.L-1) and following exercise to exhaustion (186 +/- 44 mumol.L-1 (BCAA) vs 123 +/- 19 mumol.L-1). These data demonstrate that BCAA administration in rats results in enhanced endurance performance and an increase in blood ammonia during exercise.

Glutamine supplementation prevents the decrease of mitogen response after a treadmill exercise in rats.

The effect of glutamine (Gln)-supplemented diet on mitogen response decreased immediately after a treadmill exercise was examined by measuring the proliferations of peripheral blood lymphocytes (PBL) with phytohemagglutinin (PHA) and concanavalin A (ConA) in male Fisher rats. Although the plasma Gln concentration was significantly decreased in the control group immediately after a treadmill exercise (20 m/min, 60 min) compared to rested rats, plasma Gln concentration of rats fed Gln-supplemented diet for 3 weeks was significantly higher than that of control group in resting and was not significantly decreased even immediately after a treadmill exercise. In addition, proliferation of PBL with PHA or ConA and interleukin 2 (IL2) production were also significantly decreased immediately after a treadmill exercise in control group. On the contrary, their functions were almost maintained in Gln-supplemented group even immediately after a treadmill exercise. PBL from rats fed Gln-supplemented diet showed a higher response to mitogens such as PHA and ConA compared to the control group. Furthermore, their PBL showed higher incorporation of [3H]Gln compared to that of the control group irrespective of treadmill exercise. These results indicate that the preventive effect of Gln-supplemented diet on mitogen response decreased after a treadmill exercise is due to an increased response to mitogen and increased uptake of Gln as sources of fuel and nucleotides to the immune cells.

Effects of NO synthase inhibition on the muscular blood flow response to treadmill exercise in rats

The functional role of nitric oxide (NO) release in regulating blood flow (BF) to exercising skeletal muscle was studied in conscious male Sprague-Dawley rats (603 +/- 28 g; n = 6). In this study, BF was measured using radiolabeled microspheres during treadmill exercise (10% grade, 20 m/min) before and after NO synthase (NOS) inhibition with NG-nitro-L-arginine methyl ester (30 mg/kg ia). After NOS inhibition, mean arterial blood pressure increased from resting baseline values and the duration of vasodilator responses to acetylcholine (ACh) injections (3.0 and 10.0 micrograms/kg ia) was diminished (P < 0.05), demonstrating reduced NOS function. During exercise, BF to the kidneys and organs of the gut was reduced after NOS inhibition. In addition, BF was reduced in 16 of the 28 individual hindquarter muscles or muscle parts. Moreover these reductions in BF were linearly correlated with the estimated sum of the percentage of fast-twitch oxidative glycolytic (FOG) and slow-twitch oxidative (SO) types of fibers found in each muscle [delta BF = -1.1 (%SO + %FOG) + 16.4; r = 0.88, P < 0.001]. These results suggest that NO-mediated vasodilation contributes to the BF responses within and among the muscles of the rat's hindquarters during exercise.