EFFECT OF ENDURANCE TRAINING ON HYPOTHALAMIC SEROTONIN CONCENTRATION AND PERFORMANCE

• 1 Serotonin is a neurotransmitter that modulates several functions, such as food intake, energy expenditure, motor activity, mood and sleep. Acute exhaustive endurance exercise increases the synthesis, concentration and metabolism of serotonin in the brain. This phenomenon could be responsible for central fatigue after prolonged and exhaustive exercise. However, the effect of chronic exhaustive training on serotonin is not known. The present study was conducted to examine the effect of exhaustive endurance training on performance and serotonin concentrations in the hypothalamus of trained rats.
• 2 Rats were divided into three groups: sedentary rats (SED), moderately trained rats (MOD) and exhaustively trained rats (EXT), with an increase of 200% in the load carried during the final week of training.
• 3 Hypothalamic serotonin concentrations were similar between the SED and MOD groups, but were higher in the EXT group (P < 0.05). Performance was lower in the EXT group compared with the MOD group (P < 0.05).
• 4 Thus, the present study demonstrates that exhaustive training increases serotonin concentrations in the hypothalamus, together with decreased endurance performance after inadequate recovery time. However, the mechanism underlying these changes remains unknown.

     

Effect of the Arg389Gly β(1) -adrenoceptor polymorphism on plasma renin activity and heart rate, and the genotype-dependent response to metoprolol treatment

相似文献   

Low‐intensity endurance exercise plus nandrolone decanoate modulates cardiac adiponectin and its receptors

相似文献   

Reciprocal relationship between plasma ghrelin level and arterial stiffness in hypertensive subjects

相似文献   

Modeling Circadian Rhythms of Glucocorticoid Receptor and Glutamine Synthetase Expression in Rat Skeletal Muscle

Purpose The circadian rhythm of endogenous corticosterone (CS) may produce fluctuations of downstream gene expression in normal rats. This study examined changes in glucocorticoid receptor (GR) and glutamine synthetase (GS) expression in rat skeletal muscle in relation to plasma CS over a 24-h period. Methods Fifty-four normal male Wistar rats were sacrificed at 18 time points (n = 3) over 24 h. Plasma CS concentrations and gastrocnemius muscle GR and GS mRNA and GS activity were measured. Results The circadian rhythm of plasma CS was captured by a two-harmonic function. The expression of GR and GS mRNA and GS activity follow a circadian rhythm in normal rat skeletal muscle. GR mRNA reaches a trough at 4 h after the peak of plasma CS and it fluctuates between 0.55 and 0.9 fmol g tissue⁻¹. GS mRNA and activity reach peaks at 6 and 12 h after the endogenous CS peak. GS mRNA oscillates between 3 and 6 fmol g tissue⁻¹, whereas GS activity fluctuates between 17 and 23 μmol min⁻¹ g protein⁻¹. Mechanistic receptor/gene-mediated pharmacodynamic models were applied to describe the temporal patterns of GR mRNA, GS mRNA, and GS activity within the circadian cycle. Conclusions The integrated models were able to capture the circadian expression patterns of plasma CS, and GR and GS in normal rat skeletal muscle showing a dependence of tissue gene expression on plasma CS.     

PROTECTIVE EFFECTS OF LEONURINE IN NEONATAL RAT HYPOXIC CARDIOMYOCYTES AND RAT INFARCTED HEART

• 1 Previous studies have shown that extracts of Herba leonuri, predominantly containing the phytochemical components leonurine and stachydrine, provide protective effects in the ischaemic myocardium by acting as free radical scavengers and inhibiting the formation of reactive oxygen species.
• 2 The present study was designed to investigate the cardioprotective effects of 10^?6 mol/L leonurine on neonatal rat cardiomyocytes treated with hypoxia plus serum deprivation, a component of ischaemia, and to determine the mechanisms underlying the protective effects with regard to cardiac anti‐oxidant enzymes and apoptosis genes. Cardiomyocytes were treated with leonurine 8 h prior to exposure to hypoxia. In addition, we investigated the effects of 7.5 and 15 mg/kg leonurine, administered to rats i.p. for 7 days prior to left coronary artery ligation, on subsequent infarct size of the ischaemic heart.
• 3 Leonurine significantly increased the viability of cardiomyocytes injured by hypoxia. In the leonurine‐treated group, gene expression levels of pro‐apoptotic genes, namely Bax and Fas, were significantly downregulated (by 0.95‐ and 0.72‐fold, respectively; P < 0.001) compared with the hypoxic control group, whereas the expression of Bcl‐2 and Bcl‐xl was upregulated following leonurine treatment (by 1.03‐ and 1.07‐fold, respectively; P < 0.05). Correspondingly, leonurine treatment increased Bcl‐2 protein levels and decreased Bax protein levels. Assays investigating cardiac anti‐oxidant enzymes provided further evidence for a protective effect of leonurine, as indicated by the induction of the anti‐oxidant enzymes superoxide dismutase and catalase. Furthermore, leonurine decreased infarct size in ischaemic rat heart.
• 4 The results of the present study suggest that the mechanisms of action of leonurine in hypoxic neonatal rat cardiomyocytes and infarcted rat heart may be related to its anti‐oxidant and anti‐apoptotic properties.

     

Beneficial effect of adenosine on myocardial perfusion in patients treated with primary percutaneous coronary intervention for acute myocardial infarction

相似文献   

EFFECTS OF COMBINATION THERAPY WITH PERINDOPRIL AND LOSARTAN ON LEFT VENTRICULAR REMODELLING IN PATIENTS WITH MYOCARDIAL INFARCTION

• 1 Inhibiting the renin–angiotensin–aldosterone system prevents left ventricular (LV) remodelling after myocardial infarction (MI).
• 2 The present study was designed to assess the effects of a combination of perindopril and losartan on LV remodelling, cardiac function and serum procollagen type III amino terminal peptide (PIIINP) levels in patients with acute MI.
• 3 Patients with anterior MI were divided into three groups: (i) MI + perindopril; (ii) MI + losartan; and (iii) MI + perindopril + losartan. After successful intervention therapy, perindopril (2–4 mg daily), losartan potassium (25–50 mg daily) or their combination were administered. All patients received aspirin, clopidogrel and statins, and some patients were given beta‐blockers, nitrate and a platelet glycoprotein IIb/IIIa receptor antagonist. Three months later, LV dimensions and LV ejection fraction (LVEF) were measured by ultrasonography. Plasma B‐type natriuretic peptide (BNP), serum C‐reactive protein (CRP) and PIIINP levels were evaluated using enzyme‐linked immunosorbent assay or radioimmunoassay.
• 4 The baseline characteristics of the three groups were the same. Three months after the initiation of therapy, all patients showed decreased CRP, increased BNP and PIIINP levels and LV dilation and dysfunction. Compared with the two monotherapy groups, patients in the combination group showed significantly lower CRP, BNP and PIIINP levels, less LV dilation and higher LVEF. Serum PIIINP levels were positively correlated with CRP levels (r = 0.597; P < 0.01) and LV end‐diastolic volume index (r = 0.543; P < 0.01) and were negatively correlated with LVEF (r = –0.565; P < 0.01).
• 5 For patients with acute MI, combination treatment with perindopril and losartan significantly inhibited LV remodelling and improved LV function. Inhibition of myocardial interstitial fibrosis may be part of the underlying mechanism.

     

CARDIOPROTECTIVE EFFECT OF l-GLUTAMATE IN OBESE TYPE 2 DIABETIC ZUCKER FATTY RATS

• 1 Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by l ‐glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that l ‐glutamate‐mediated postischaemic cardioprotection mimics IPC.
• 2 Rat hearts were studied in a Langendorff preparation perfused with Krebs’–Henseleit solution and subjected to 40 min global no‐flow ischaemia, followed by 120 min reperfusion. l ‐Glutamate (0, 15 and 30 mmol/L) was added to the perfusate during reperfusion of hearts from non‐diabetic (Wistar‐Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area‐at‐risk (AAR) ratio was the primary end‐point. Expression of l ‐glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative polymerase chain reaction and immunoblotting.
• 3 The ISS/AAR ratio did not differ between control hearts from Wistar‐Kyoto and ZDF rats (0.52 ± 0.03 and 0.51 ± 0.04, respectively; P = 0.90). l ‐Glutamate (15 mmol/L) significantly reduced the IS/AAR ratio in non‐diabetic hearts, but not in diabetic hearts, compared with their respective controls. The higher concentration of l ‐glutamate (30 mmol/L) reduced infarct size in diabetic hearts to the same degree as in non‐diabetic hearts (IS/AAR 0.35 ± 0.03 (P = 0.002) and 0.34 ± 0.03 (P = 0.004), respectively). The mitochondrial l ‐glutamate transporter EAAT1 was downregulated in hearts from ZDF rats at both the mRNA and protein levels (P < 0.0005 and P < 0.0001, respectively). However, there was no change in EAAT3 expression at the protein level. Myocardial l ‐glutamate content was increased by 43% in diabetic hearts (P < 0.0001).
• 4 Hearts from obese diabetic rats have an elevated threshold for metabolic postischaemic cardioprotection by l ‐glutamate. These findings may reflect underlying mechanisms of inherent resistance against additional cardioprotection in the diabetic heart.

     

Routine early versus deferred provisional tirofiban treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention

相似文献   

EFFECTS OF EMULSIFIED ISOFLURANE ON HAEMODYNAMICS AND CARDIOMYOCYTE APOPTOSIS IN RATS WITH MYOCARDIAL ISCHAEMIA

• 1 It has been shown that inhaled isoflurane limits the size of myocardial infarcts. The aim of the present study was to examine the effects of emulsified isoflurane on cardiac function and myocardial apoptosis in an ischaemia model of myocardial injury.
• 2 In the first study, 48 rats were randomly allocated to six groups (n = 8 in each): control (saline); emulsified isoflurane (EIso) at 1, 2 or 4 mL/kg; 30% intralipid (vehicle for EIso); and sham operated. Rats received isovolumetric intravenous infusions for 30 min and then, 30 min after cessation of the infusion, 90 min coronary occlusion. Haemodynamics and myocardial infarct size were measured. In the second study, another 48 rats were randomized into six groups (n = 8 in each). After 90 min ischaemia, rats were killed for histopathological study, immunohistochemical evaluation and apoptosis measurement.
• 3 Pretreatment with 2 and 4 mL/kg EIso significantly attenuated decreases in left ventricular systolic pressure and dP/dt_max, and increases in left ventricular end‐diastolic pressure and –dP/dp_max, and alleviated myocardial injury compared with the control, intralipid and 1 mL/kg EIso groups (P < 0.05). Infusion of 1 mL/kg EIso and intralipid had no effect on haemodynamics, infarct size or histological variables.
• 4 Expression of Bcl‐2 was increased, whereas expression of Bax and caspase 3 was decreased, after preconditioning with 2 and 4 mL/kg EIso (P < 0.05). The apoptotic index in the 2 and 4 mL/kg Eiso‐treated groups was reduced compared with that in the control and intralipid groups (P < 0.01).
• 5 In conclusion, EIso ameliorates cardiac dysfunction, attenuates myocardial damage and inhibits apoptosis after ischaemia, which may be attributed, in part, to diminished expression of apoptosis‐related protein.

     

Physical exercise and binding of digoxin to skeletal muscle — Effect of muscle activation frequency

Summary Ten healthy subjects who had ingested 0.5 mg digoxin daily for at least 10 days, performed a 1-hour bicycle exercise test on two occasions, 24 h after the latest dose, with the same work load but at two different pedalling rates, 40 and 80 rpm. During exercise the mean digoxin concentration in the thigh muscle increased by 8% at 40 rpm (n.s.) and by 29% at 80 rpm (p<0.01). The serum digoxin concentration decreased by 39% at both pedalling rates (p<0.001). The results suggest that the increase in skeletal muscle digoxin concentration during exercise is related to the neuromuscular activation frequency. The digoxin concentration in erythrocytes was measured in 16 healthy subjects before and 1 minute after a 1-hour bicycle exercise test. The erythrocyte digoxin concentration decreased by 12% (p<0.01) during the exercise indicating that the increased uptake of digoxin in skeletal muscle during exercise influences the digoxin concentration in other tissues.     

ACUTE EFFECTS OF NICOTINE ON ARTERIAL STIFFNESS AND WAVE REFLECTION IN HEALTHY YOUNG NON-SMOKERS

• 1 Recently, we have demonstrated that cigarette smoke exposure proportionally increases plasma nicotine levels and arterial wave reflection to the aorta. However, the exact contribution of nicotine to the smoke‐induced enhancement of wave reflection and the potential underlying mechanisms have not been fully investigated.
• 2 The present study was a prospective study in 15 healthy male non‐smokers. All received a placebo and a 2 mg nicotine tablet, according to a randomized double‐blind cross‐over study design. Each subject underwent repeated measurements at baseline and for 1 h after nicotine or placebo intake, using carotid–femoral pulse wave velocity (PWV) to assess arterial compliance. Concurrently, aortic pressures and the augmentation index were evaluated using applanation tonometry.
• 3 Plasma nicotine concentrations achieved 1 h after intake of the nicotine tablet reached comparable levels to those achieved after 1 h exposure to passive smoke (3.6 ± 0.4 vs 3.2 ± 0.4 ng/mL, respectively; P = 0.4).
• 4 Nicotine enhanced arterial wave reflection to the aorta, as assessed by the augmentation index corrected for heart rate (4.2 ± 1.3 vs–0.7 ± 0.8% with placebo; P = 0.001). In addition, a progressive increase in carotid–femoral PWV was noted after nicotine administration (0.3 ± 0.1 vs–0.02 ± 0.1 m/s with placebo; P = 0.04). This remained significant even after adjustment for changes in mean blood pressure and heart rate (P = 0.01).
• 5 Plasma nicotine concentrations comparable to those achieved after exposure to passive smoke enhance arterial wave reflection to the aorta. This is accompanied by an increase in carotid–femoral PWV, denoting a deterioration of arterial compliance by nicotine.

     

ENDOPLASMIC RETICULUM STRESS INVOLVED IN HEART AND LIVER INJURY IN IRON-LOADED RATS

• 1 Iron overload contributes to the pathogenesis of various diseases and directly induces tissue injury. In the present study, we investigated the relationship between heart and liver injury induced by iron overload and cellular endoplasmic reticulum (ER) stress to explore the molecular mechanism of iron overload‐induced cellular injury.
• 2 Iron overload in rats was generated by intraperitoneal injection of iron–dextran chronically (30 mg/kg per day for 9 weeks) or acutely (300 mg/kg once). Tissue injury was assessed by determining serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as malondialdehyde (MDA) content in the heart and liver. The ER stress response was analysed by expression of glucose‐response protein 78 (GRP78) and activation of caspase 12.
• 3 In chronic iron‐loaded rats, iron levels in the heart and liver were higher, by approximately 2‐and 7.8‐fold, respectively (P < 0.01), compared with control. Serum LDH, ALT and AST activity, as well as MDA content, GRP78 expression and caspase 12 activity in the heart and liver, were upregulated in chronically iron‐loaded rats. In acute iron‐loaded rats, iron content in the heart and liver was 51% and 63% higher than in controls (both P < 0.01). Serum LDH, ALT and AST activity, MDA content in the heart and liver and levels of ER stress markers were all increased in acute iron‐loaded rats. N‐Acetylcysteine (150 mg/kg, s.c.) lowered the levels of these parameters in acute iron‐loaded rats.
• 4 The results of the present study indicate that ER stress may play an important role in iron‐induced tissue injury and that reactive oxygen species may mediate the ER stress response in the pathogenesis of iron‐overload cellular injury.

     

Pretreatment with clonidine caused desensitization to WIN 55,212‐2 in guinea pig ileum

相似文献   

Exercise training upregulates nitric oxide synthases in the kidney of rats with chronic heart failure

相似文献   

Identification of differentially expressed proteins related to organophosphorus‐induced delayed neuropathy in the brains of hens

Some organophosphorus compounds can cause organophosphate‐induced delayed neuropathy (OPIDN). Incidents have been documented for decades, however, little is known about which proteins contribute to the initiation, progression and development of OPIDN. In this study, 51 hens were divided into three groups. The tri‐ortho‐cresyl‐phosphate (TOCP) group was treated with 1000 mg kg^–1 TOCP whereas the control group was treated with an equivalent volume of vehicle. The PMSF + TOCP group was treated subcutaneously with 40 mg kg^–1 phenylmethylsulfonyl fluoride (PMSF), followed by 1000 mg kg^–1 TOCP 24 h later. Proteins in the brains of hens were separated by two‐dimensional polyacrylamide gel electrophoresis on day 5 after TOCP administration. Mass spectrometry identified eight differentially expressed proteins. Among these proteins, downregulated expression of glutamine synthetase (GS) in the brains of hens after TOCP treatment was further confirmed by real time RT‐PCR and ELISA. Moreover, the brains of hens exposed to TOCP exhibited increased levels of glutamate (Glu) and cytosolic calcium concentration ([Ca²⁺]_i), and a decreased level of glutamine (Gln). However, there were no significant differences in GS expression or levels of Glu, Gln, and [Ca²⁺]_i in the brains of hens among the groups on day 21 after TOCP administration. These results indicate that TOCP exposure downregulates GS expression in the brains of hens, and that downregulation of GS is accompanied by increased levels of Glu and [Ca²⁺]_i in the early stage after TOCP administration. It is also suggested that the downregulated expression of GS might be associated with OPIDN through the disruption of homeostasis of the Glu–Gln cycle and [Ca²⁺]_i. Copyright © 2013 John Wiley & Sons, Ltd.     

Fibroblast growth factor 23 is associated with the presence of coronary artery disease and the number of stenotic vessels

Fibroblast growth factor 23 (FGF23) has been reported to be involved in cardiovascular disease. The aim of this study was to investigate the association between FGF23 and the presence of coronary artery disease (CAD), as well as the number of stenotic vessels. A total of 254 eligible participants (167 men and 87 postmenopausal women) were enrolled in this study. Coronary angiography was used for diagnosis of CAD. Serum intact FGF23 levels were determined by a two‐sided sandwich enzyme‐linked immunosorbent assay. The median serum FGF23 levels of the entire study population were 39.9 (33.1–47.5) pg/mL. Serum FGF23 levels were higher in subjects with one‐vessel disease than those without CAD (P < 0.05), which further increased significantly in the subjects with multi‐vessel disease (P < 0.05). Serum FGF23 levels increased with cumulative number of stenotic vessels (P for trend < 0.001). Multiple stepwise regression analysis revealed estimated glomerular filtration rate (standardized β = ?0.298; P < 0.001) and body mass index (standardized β = 0.132; P = 0.049) were independent factors correlated with FGF23. Multivariate logistic regression analysis showed that FGF23 was positively and independently associated with the presence of CAD (odds ratio = 1.058, 95% confidence interval = 1.025–1.092; P = 0.001). Additionally, FGF23 was also correlated with multi‐vessel disease significantly (odds ratio = 1.034, 95% confidence interval = 1.007–1.062; P = 0.013). In conclusion, serum FGF23 levels exhibit positive and independent association with the presence of CAD and increase with the cumulative number of stenotic vessels.