Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was to evaluate the effects of nitric oxide (NO) on diaphragmatic fatigue in fifteen anaesthetized, mechanically ventilated pigs, divided into three groups. The animals were pre-treated with indomethacin (3 mg kg-1, i.v.) to block the cyclo-oxygenase pathway. To group 1 pigs (n = 6) NG-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1 i.v.) was administered as a bolus to block endogenous NO production, while group 2 pigs (n = 6) were infused with sodium nitroprusside (SNP, 0.023 mg kg-1, i.v.), a donor of NO. Group 3 pigs (n = 3) were used as the controls. We evaluated diaphragmatic strength by measuring the transdiaphragmatic pressure (P di) generated during bilateral phrenic nerve stimulation at 10, 20, 30 and 50 Hz, 15 V, while the diaphragmatic endurance was assessed by a 30s stimulation at 10 Hz, 15 V. Diaphragmatic index was assessed as the ratio of peak force between single twitches performed before and after the 30 s stimulation west. We also evaluated mean systemic (MAP) and pulmonary (MPAP) arterial pressures, pulmonary wedge pressure (PW), systemic (SVR) and pulmonary vascular resistance (PVR) and cardiac output (CO). L-NAME increased MAP, MPAP, PW, SVR and PVR, but decreased CO. SNP caused a decrease in MAP, MPAP, PW and SVR, while PVR and CO did not change. The main finding of this study was that diaphragmatic strength was not significantly weakened after L-NAME administration, except at 10 Hz, while it did not change after SNP infusion. However, both L-NAME and SNP caused significant decreases in diaphragmatic endurance capacity. The fatigue appearing after L-NAME is probably correlated with a decline in diaphragmatic blood flow, as evidenced by the increase in SVR and the decrease in CO, and consequently in oxygen supply. In contrast, the decrease in endurance capacity after SNP infusion can be attributed to a direct action of NO on skeletal muscle.
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PMID:Effects of nitric oxide on diaphragmatic muscle endurance and strength in pigs. 902 9

The role of endogenous nitric oxide (NO) in producing diaphragmatic fatigue was examined in 26 anaesthetized, mechanically ventilated dogs divided into four groups. In Group Ia (n = 5), dogs without fatigue received only Ringer's lactate solution. In Group Ib (n = 5), dogs without fatigue were given i.v. L-arginine analog N omega-nitro-L-arginine methyl ester (L-NAME) 10 mg.kg-1 to inhibit NO synthase (NOS). Groups IIa and IIb (n = 8 of each) received the same doses of i.v. lactate and L-NAME as Groups Ia and Ib effectively. Following administration of the i.v. solution, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed in each group by measuring transdiaphragmatic pressure (Pdi). No difference in Pdi was observed between Groups Ia and Ib. After the fatigue-producing period, in Group IIa, Pdi at low-frequency (20 Hz) stimulation decreased from the pre-fatigued values (P < 0.05), whereas Pdi at high-frequency (100 Hz) stimulation did not change. In Group IIb, given L-NAME before producing fatigue, Pdi at both stimuli did not change. In conclusion, L-NAME inhibits the production of diaphragmatic fatigue. This finding suggests that endogenous NO plays an important role in producing diaphragmatic fatigue.
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PMID:Protection from diaphragmatic fatigue by nitric oxide synthase inhibitor in dogs. 2357 74

Studies of the effect of nitric oxide (NO) synthesis inhibition were performed in the isometrically contracting blood-perfused canine gastrocnemius-plantaris muscle group. Muscle blood flow (Q) was controlled with a pump during continuous NO blockade produced with either 1 mM L-argininosuccinic acid (L-ArgSA) or N(G)-nitro-L-arginine methyl ester (L-NAME) during repetitive tetanic contractions (50-Hz trains, 200-ms duration, 1/s). Pump Q was set to match maximal spontaneous Q (1.3-1.4 ml. min(-1). g(-1)) measured in prior, brief (3-5 min) control contraction trials in each muscle. Active tension and oxygen uptake were 500-600 g/g and 200-230 microl. min(-1). g(-1), respectively, under these conditions. Within 3 min of L-ArgSA infusion, vascular resistance across the muscle (R(v)) increased significantly (from approximately 100 to 300 peripheral resistance units; P < 0.05), whereas R(v) increased to a lesser extent with L-NAME (from approximately 100 to 175 peripheral resistance units; P < 0.05). The increase in R(v) with L-ArgSA was unchanged by simultaneous infusion of 0.5-10 mM L-arginine but was reduced with 1-3 microg/ml sodium nitroprusside (41-54%). The increase in R(v) with L-NAME was reversed with 1 mM of L-arginine. Increased fatigue occurred with infusion of L-ArgSA; active tension and intramuscular pressure decreased by 62 and 66%, whereas passive tension and baseline intramuscular pressure increased by 80 and 30%, respectively. These data indicate a possible role for NO in the control of R(v) and contractility within the canine gastrocnemius-plantaris muscle during repetitive tetanic contractions.
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PMID:Influence of nitric oxide on vascular resistance and muscle mechanics during tetanic contractions in situ. 1040 68

Extraocular muscles (EOMs) are specialized skeletal muscles that are constantly active, generate low levels of force for cross sectional area, have rapid contractile speeds, and are highly fatigue resistant. The neuronal isoform of nitric oxide synthase (nNOS) is concentrated at the sarcolemma of fast-twitch muscles fibers, and nitric oxide (NO) modulates contractility. This study evaluated nNOS expression in EOM and the effect of NO modulation on lateral rectus muscle's contractility. nNOS activity was highest in EOM compared with diaphragm, extensor digitorum longus, and soleus. Neuronal NOS was concentrated to the sarcolemma of orbital and global singly innervated fibers, but not evident in the multi-innervated fibers. The NG-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor), increased submaximal tetanic and peak twitch forces. The NO donors S-nitroso-N-acetylcysteine (SNAC) and spermineNONOate reduced submaximal tetanic and peak twitch forces. The effect of NO on the contractile force of lateral rectus muscle is greater than previously observed on other skeletal muscle. NO appears more important in modulating contraction of EOM compared with other skeletal muscles, which could be important for the EOM's specialized role in generation of eye movements.
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PMID:Nitric oxide synthase expression and effects of nitric oxide modulation on contractility of rat extraocular muscle. 1148 Dec 24

1. Panax ginseng is used to enhance stamina and relieve fatigue as well as physical stress. Ginsenoside, the effective component of ginseng, regulates cardiovascular function. This study was to examine the effect of ginsenosides Rb1 and Re on cardiac contractile function at the cellular level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz. Contractile properties analysed included: peak shortening (PS), time-to-90%PS (TPS), time-to-90% relengthening (TR90), and fluorescence intensity change (DeltaFFI). Nitric oxide synthase (NOS) activity was determined by the 3H-arginine to 3H-citrulline conversion assay. 2. Both Rb1 and Re exhibited dose-dependent (1-1000 nM) inhibition in PS and DeltaFFI, with maximal inhibitions between 20-25%. Concurrent application Rb1 and Re did not produce any additive inhibition on peak shortening amplitude (with a maximal inhibition of 24.9+/-6.1%), compared to Rb1 or Re alone. Pretreatment with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) abolished the effect of Rb1 and Re. Both Rb1 and Re significantly (P<0.05) stimulated NOS activity concentration-dependently. 3. This study demonstrated a direct depressant action of ginsenosides on cardiomyocyte contraction, which may be mediated in part through increased NO production.
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PMID:Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide. 1170 35

Nitric oxide (NO) has an inhibitory action on O2 uptake (VO2) at the level of the mitochondrial respiratory chain. The aim of this study was to evaluate the effects of NO synthase (NOS) inhibition on muscle (VO2) kinetics. Isolated canine gastrocnemius muscles in situ (n = 6) were studied during transitions from rest to 4-min of electrically stimulated contractions corresponding to approximately 60% of the muscle peak . Two conditions were compared: (i) Control (CTRL) and (ii) L-NAME, in which the NOS inhibitor L-NAME (20 mg kg(-1)) was administered. In both conditions the muscle was pump-perfused with constantly elevated blood flow (Q), at a level measured during a preliminary contraction trial with spontaneous self-perfused (Q). A vasodilatory drug was also infused. Arterial and venous O2 concentrations were determined at rest and at 5-7 s intervals during the transition. VO2 was calculated by Fick's principle. Muscle biopsies were obtained at rest and during contractions. Muscle force was measured continuously. Phosphocreatine hydrolysis and the calculated substrate level phosphorylation were slightly (but not significantly) lower in L-NAME than in CTRL. Significantly (P < 0.05) less fatigue was found in L-NAME versus CTRL. The time delay (TD(f)) and the time constant (tau(f)) of the 'fundamental' component of VO2 kinetics were not significantly different between CTRL (TD(f) 7.2 +/- 1.2 s; and tau(f) 10.6 +/- 1.3, +/- s.e.m.) and L-NAME (TD(f) 9.3 +/- 0.6; and tau(f) 10.4 +/- 1.0). Contrary to our hypothesis, NOS inhibition did not accelerate muscle VO2 kinetics. The down-regulation of mitochondrial respiration by NO does not limit the kinetics of adjustment of oxidative metabolism at exercise onset.
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PMID:Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ. 1675 29

To assess the role of nitric oxide (NO) in central thermoregulatory mechanisms during exercise, 1.43 micromol (2 microL) of N(omega)-nitro-L-arginine methyl ester (L-NAME, n=6), a NO synthase inhibitor, or 2 microL of 0.15M NaCl (SAL, n=6) was injected into the lateral cerebral ventricle of male Wistar rats immediately before the animals started running (18 m min(-1), 5% inclination). Core (Tb) and skin tail (Ttail) temperatures were measured. Body heating rate (BHR), threshold Tb for tail vasodilation (TTbV), and workload (W) were calculated. During the first 11 min of exercise, there was a greater increase in Tb in the L-NAME group than in the SAL group (BRH=0.17+/-0.02 degrees C min(-1), L-NAME, versus 0.09+/-0.01 degrees C min(-1), SAL, p<0.05). Following the first 11 min until approximately 40 min of exercise, Tb levels remained stable in both groups, but levels remained higher in the L-NAME group than in the SAL group (39.16+/-0.04 degrees C, L-NAME, versus 38.33+/-0.02 degrees C, SAL, p<0.01). However, exercise went on to induce an additional rise in Tb in the SAL group prior to fatigue. These results suggest that the reduced W observed in L-NAME-treated rats (10.8+/-2.0 kg m, L-NAME, versus 25.0+/-2.1 kg m, SAL, p<0.01) was related to the increased BHR in L-NAME-treated animals observed during the first 11 min of exercise (r=0.74, p<0.01) due to the change in TTbV (39.12+/-0.24 degrees C, L-NAME, versus 38.27+/-0.10 degrees C, SAL, p<0.05). Finally, our data suggest that the central nitric oxide pathway modulates mechanisms of heat dissipation during exercise through an inhibitory mechanism.
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PMID:Nitric oxide pathway is an important modulator of heat loss in rats during exercise. 1614 Jan 69

To assess the role of nitric oxide (NO) in the metabolic rate and running performance of rats submitted to exercise on a treadmill, 1.43 micromol (2 microL) of Nomega-nitro-L-arginine methyl ester (L-NAME, n=6), a NO synthase inhibitor, or 2 microL of 0.15M NaCl (SAL, n=6) was injected into the lateral cerebral ventricle of male Wistar rats immediately before the animals started running (18m min(-1), 5% inclination). Oxygen consumption (VO2) was measured at rest, during the exercise until fatigue and thereafter during the 30 min of recovery using the indirect calorimetry system. Mechanical efficiency (ME) was also calculated during the running period. During the first 11 min of exercise, there was a similar increase in VO2 while ME remained the same in both groups. Thereafter, VO2 remained stable in the SAL group but continued to increase and remained higher in the L-NAME group until fatigue. The L-NAME-treated rats also showed a sharper decrease in ME than controls. In addition, there was a significant reduction in workload performance by L-NAME-treated animals compared to SAL-treated animals. This suggests that central blockage of nitric oxide increases metabolic cost during exercise, reduces mechanical efficiency and decreases running performance in rats.
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PMID:Evidence that brain nitric oxide inhibition increases metabolic cost of exercise, reducing running performance in rats. 1627 31

The influence of the central nervous system on metabolic function is of interest in situations deviating from basal states, such as during exercise. Our previous study in rats demonstrated that central nitric oxide (NO) blockade increases metabolic rate, reducing mechanical efficiency during exercise. To assess the role of brain nitric oxide in the plasma glucose, lactate and free fatty acids (FFAs) concentrations of rats submitted to an incremental exercise protocol on a treadmill until fatigue, 1.43 micromol (2 microl) of N(omega)-nitro-l-arginine methyl ester (L-NAME, n=6), a NO synthase inhibitor, or 2 microl of 0.15M NaCl (SAL, n=6) was injected into the lateral cerebral ventricle (icv) of male Wistar rats immediately before exercise (starting at 10 m/min, with increments of 1m/min every 3 min until fatigue, 10% inclination). Blood samples were collected through a chronic jugular catheter at rest and during exercise until fatigue. During exercise, the L-NAME-treated animals had the following metabolic response compared to controls: (1) an increased hyperglycemic response during the first 60% of time to fatigue; (2) higher plasma lactate levels; and (3) a significant transitory increase in plasma free fatty acids during the dynamic phase of exercise that returned to basal levels earlier than controls during the steady state phase of exercise. In addition L-NAME-treated rats fatigued earlier than controls. The data indicate that the inhibition of the brain nitrergic system induced by icv L-NAME treatment disrupted the accuracy of the neural mechanism that regulates plasma glucose and free fatty acids mobilization during exercise in rats.
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PMID:Central nitric oxide inhibition modifies metabolic adjustments induced by exercise in rats. 1708 69

Caffeine (Caf) is largely used to delay fatigue, improving physical activity. However, its role remains elusive, and there are no hemodynamic or immunohistochemical data regarding its effects on skeletal muscle. We studied the hemodynamic and NOS expression of Bax/Bcl2 in skeletal muscle after single Caf administration. Thirty-two male rats were divided into six groups: the first was iv-injected with Caf (16mg/kg), the second with Caf+L-NAME, the third with Caf+L-arg, the fourth with Caf+L-NAME+L-arg, fifth with saline. Mean arterial blood pressure (MAP) was monitored for 30', then the animals were killed. The sixth group was injected with Caf and killed after 2h. The quadriceps were isolated and processed by immunohistochemistry. We found that Caf increased MAP temporarily, while Caf+L-NAME increased it for a longer period. In untreated muscle, all NOS isoforms was expressed with different intensity and localisation, and Bcl2 was strongly expressed among the myofibrils. In Caf and Caf+L-NAME treated animals, NOS expression was lost; Bcl2 expression decreased among myofibrils but increased inside the subsarcolemma. The L-arg administration reversed these Caf and L-NAME effects. Two hours after Caf, NOS expression increased. We concluded that improved physical performance could be related to Caf's ability to interfere with the endogenous muscular synthesis of NO.
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PMID:Acute caffeine administration decreased NOS and Bcl2 expression in rat skeletal muscles. 1723 87


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