Effect of exercise duration on plasma endothelin-1 concentration.

AIM: Endothelin-1 (ET-1) is a potent vasoconstricting peptide released mostly from vascular endothelial cells. Isolated exercise sessions of relatively long duration (=or>30 min) have produced increases in plasma ET-1 concentration while shorter exercise sessions usually have not. The purpose of the present study was to verify an effect of exercise duration at a steady work rate on plasma ET-1 concentration. METHODS: Eleven endurance-trained males (age 27+/-6 years; maximal oxygen consumption--VO2max--56+/-7 mLxkg-1xmin-1, body fat 11+/-5%; mean+/-SD) exercised on a treadmill at 70% VO2max on 2 occasions separated by at least 2 weeks. During a short-duration session, subjects expended approximately 3,360 kJ (60+/-2 min). During a long-duration session, subjects expended approximately 6,300 kJ (112+/-4 min). Six of the subjects performed the 3,360 kJ session before the 6,300 kJ session while the other 5 subjects performed the 6,300 kJ session first. RESULTS: The short-duration session did not cause plasma ET-1 concentration to change immediately after exercise (0.23+/-0.01 pmolxL-1 before exercise, 0.22+/-0.02 pmolxL-1 after exercise, mean+/-SE). However, 10 of 11 subjects had increased ET-1 after the long-duration session (0.28+/-0.02 pmolxL-1 before exercise, 0.32+/-0.02 pmolxL-1 after exercise, P=0.0004). A treatment-by-time effect was present (P=0.003). CONCLUSION: These results demonstrate an effect of exercise duration on plasma ET-1 concentration. Exercise duration is, therefore, an essential consideration when investigating exercise's effect on ET-1.

Effect of antioxidants and ACE inhibition on chemical modification of proteins and progression of nephropathy in the streptozotocin diabetic rat.

AIMS/HYPOTHESIS: This study was designed to determine whether inhibition of formation of AGE and advanced lipoxidation end-products (ALE) is a mechanism of action common to a diverse group of therapeutic agents that limit the progress of diabetic nephropathy. We compared the effects of the ACE inhibitor enalapril, the antioxidant vitamin E, the thiol compound lipoic acid, and the AGE/ALE inhibitor pyridoxamine on the formation of AGE/ALE and protection against nephropathy in streptozotocin diabetic rats. METHODS: Renal function and AGE/ALE formation were evaluated in rats treated with the agents listed above. Plasma was monitored monthly for triglycerides, cholesterol, creatinine and TNF-alpha, and 24-h urine samples were collected for measurement of albumin and total protein excretion. After 29 weeks, renal expression of mRNA for extracellular matrix proteins was measured, and AGE/ALE were quantified in skin and glomerular and tubular collagen. RESULTS: Diabetic animals were both hyperglycaemic and dyslipidaemic, and showed evidence of early nephropathy (albuminuria, creatinaemia). All interventions limited the progression of nephropathy, without affecting glycaemia. The order of efficacy was: pyridoxamine (650 mg.kg(-1).day(-1)) > vitamin E (200 mg.kg(-1).day(-1)) > lipoic acid (93 mg.kg(-1).day(-1)) approximately enalapril (35 mg.kg(-1).day(-1)). Pyridoxamine also significantly inhibited AGE/ALE accumulation in tissues; effects of other agents were mixed, but the degree of renoprotection was consistent with their effects on AGE/ALE formation. CONCLUSIONS/INTERPRETATION: All interventions inhibited the progression of nephropathy at the doses studied, but the maximal benefit was achieved with pyridoxamine, which also limited dyslipidaemia and AGE/ALE formation. These experiments indicate that the more effective the renoprotection, the greater the inhibition of AGE/ALE formation. For optimal protection of renal function, it would be beneficial to select drugs whose mechanism of action includes inhibition of AGE/ALE formation.

Simple non-invasive assessment of advanced glycation endproduct accumulation.

AIMS/HYPOTHESIS: The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. METHODS: Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL). RESULTS: Autofluorescence correlated with CLF, pentosidine, CML, and CEL ( r=0.47-0.62, p

Role of lipids in chemical modification of proteins and development of complications in diabetes.

Hyperglycaemia is the major risk factor for the development of complications in both Type I and Type II diabetes; however, there is growing evidence from several clinical trials that dyslipidaemia, including hypertriglyceridaemia, is a significant and independent risk factor for diabetic complications. In this paper, we propose that chemical modification of proteins by lipids may be a underlying pathogenic mechanism linking dyslipidaemia to diabetic complications. Thus the major AGEs (advanced glycation end-products) in tissues, such as carboxymethyl-lysine, carboxyethyl-lysine and hydroimidazolones, may, in fact, be ALEs (advanced lipoxidation end-products), derived from lipids. Increased lipid peroxidation and accelerated ALE formation, possibly catalysed by hyperglycaemia and oxidative stress, may be the mechanistic link between dyslipidaemia and diabetic complications. If correct, this proposal would suggest that inhibition or reversal of glycation, which is a central theme of this symposium, may not be sufficient for protection against diabetic complications.

Plasma lipid and lipoprotein responses during exercise.

The purpose of this study was to examine the effect of prolonged exercise on plasma lipid and lipoprotein concentrations and to identify caloric time-points where changes occurred. Eleven active male subjects ran on a treadmill at 70% of maximal fitness (VO2max) and expended 6278.7 kilojoules (Kj) energy (1500 kcal). Blood samples were obtained at the 4185.8 Kj (1000 kcal) timepoint during exercise and at each additional 418.6 Kj (100 kcal) expenditure until 6278.7 Kj was expended. After correcting for plasma volume changes, decreases in low-density lipoprotein cholesterol (LDL-C) were observed during exercise at time-points corresponding to 4604.4 and 5441.5 Kj (1100 and 1300 kcal) of energy expenditure, and immediately after exercise. Total cholesterol concentrations decreased significantly at exercise kilojoule expenditures of 4604.4, 5441.5 and 5860.1 (1100, 1300 and 1400 kcal). There were also exercise induced increases in high-density lipoprotein cholesterol (HDL-C) and HDL2-C concentrations immediately after exercise. Although acute lipid and lipoprotein changes are typically reported in the days following exercise, the current data indicate that some lipoprotein concentrations change during acute exercise. Our data suggest that a threshold of exercise may be necessary to change lipoproteins during exercise. Future work should identify potential mechanisms (lipoprotein lipase, cholesterol ester transport protein, LDL uptake) that alter lipoprotein concentrations during prolonged exercise.

Blood lipid and lipoprotein adaptations to exercise: a quantitative analysis.

Dose-response relationships between exercise training volume and blood lipid changes suggest that exercise can favourably alter blood lipids at low training volumes, although the effects may not be observable until certain exercise thresholds are met. The thresholds established from cross-sectional literature occur at training volumes of 24 to 32 km (15 to 20 miles) per week of brisk walking or jogging and elicit between 1200 to 2200 kcal/wk. This range of weekly energy expenditure is associated with 2 to 3 mg/dl increases in high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) reductions of 8 to 20 mg/dl. Evidence from cross-sectional studies indicates that greater changes in HDL-C levels can be expected with additional increases in exercise training volume. HDL-C and TG changes are often observed after training regimens requiring energy expenditures similar to those characterised from cross-sectional data. Training programmes that elicit 1200 to 2200 kcal/wk in exercise are often effective at elevating HDL-C levels from 2 to 8 mg/dl, and lowering TG levels by 5 to 38 mg/dl. Exercise training seldom alters total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C). However, this range of weekly exercise energy expenditure is also associated with TC and LDL-C reductions when they are reported. The frequency and extent to which most of these lipid changes are reported are similar in both genders, with the exception of TG. Thus, for most individuals, the positive effects of regular exercise are exerted on blood lipids at low training volumes and accrue so that noticeable differences frequently occur with weekly energy expenditures of 1200 to 2200 kcal/wk. It appears that weekly exercise caloric expenditures that meet or exceed the higher end of this range are more likely to produce the desired lipid changes. This amount of physical activity, performed at moderate intensities, is reasonable and attainable for most individuals and is within the American College of Sports Medicine's currently recommended range for healthy adults.

Effects of short-duration and long-duration exercise on lipoprotein(a).

PURPOSE: Most studies that use either a single exercise session, exercise training, or a cross-sectional design have failed to find a relationship between exercise and plasma lipoprotein(a) [Lp(a)] concentrations. However, a few studies investigating the effects of longer and/or more strenuous exercise have shown elevated Lp(a) concentrations, possibly as an acute-phase reactant to muscle damage. Based on the assumption that greater muscle damage would occur with exercise of longer duration, the purpose of the present study was to determine whether exercise of longer duration would increase Lp(a) concentration and creatine kinase (CK) activity more than exercise of shorter duration. METHODS: Ten endurance-trained men (mean +/- SD: age, 27 +/- 6 yr; maximal oxygen consumption [VO(2max)], 57 +/- 7 mL x kg(-1) x min(-1)) completed two separate exercise sessions at 70% VO(2max). One session required 800 kcal of energy expenditure (60 +/- 6 min), and the other required 1500 kcal (112 +/- 12 min). Fasted blood samples were taken immediately before (0-pre), immediately after (0-post), 1 d after (1-post), and 2 d after (2-post) each exercise session. RESULTS: CK activity increased after both exercise sessions (mean +/- SE; 800 kcal: 0-pre 55 +/- 11, 1-post 168 +/- 64 U x L(-1) x min(-1); 1500 kcal: 0-pre 51 +/- 5, 1-post 187 +/- 30, 2-post 123 +/- 19 U x L(-1) x min(-1); P < 0.05). However, median Lp(a) concentrations were not altered by either exercise session (800 kcal: 0-pre 5.0 mg x dL(-1), 0-post 3.2 mg x dL(-1), 1-post 4.0 mg x dL(-1), 2-post 3.4 mg x dL(-1); 1500 kcal: 0-pre 5.8 mg x dL(-1), 0-post 4.3 mg x dL(-1), 1-post 3.2 mg x dL(-1), 2-post 5.3 mg x dL(-1)). In addition, no relationship existed between exercise-induced changes in CK activity and Lp(a) concentration (800 kcal: r = -0.26; 1500 kcal: r = -0.02). CONCLUSION: These results suggest that plasma Lp(a) concentration will not increase in response to minor exercise-induced muscle damage in endurance-trained runners.

Serotonin and central nervous system fatigue: nutritional considerations.

Fatigue from voluntary muscular effort is a complex phenomenon involving the central nervous system (CNS) and muscle. An understanding of the mechanisms within muscle that cause fatigue has led to the development of nutritional strategies to enhance performance. Until recently, little was known about CNS mechanisms of fatigue, even though the inability or unwillingness to generate and maintain central activation of muscle is the most likely explanation of fatigue for most people during normal daily activities. A possible role of nutrition in central fatigue is receiving more attention with the development of theories that provide a clue to its biological mechanisms. The focus is on the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] because of its role in depression, sensory perception, sleepiness, and mood. Nutritional strategies have been designed to alter the metabolism of brain 5-HT by affecting the availability of its amino acid precursor. Increases in brain 5-HT concentration and overall activity have been associated with increased physical and perhaps mental fatigue during endurance exercise. Carbohydrate (CHO) or branched-chain amino acid (BCAA) feedings may attenuate increases in 5-HT and improve performance. However, it is difficult to distinguish between the effects of CHO on the brain and those on the muscles themselves, and most studies involving BCAA show no performance benefits. It appears that important relations exist between brain 5-HT and central fatigue. Good theoretical rationale and data exist to support a beneficial role of CHO and BCAA on brain 5-HT and central fatigue, but the strength of evidence is presently weak.

Delayed effects of exercise on the plasma leptin concentration.

Recent studies have concluded that a single exercise session has no immediate effect on the plasma concentration of leptin, a putative satiety factor. We tested the hypothesis that an increase in energy expenditure would decrease the leptin concentration but the effects would be manifest in a 48-hour period following exercise. Eleven active males completed two treadmill exercise sessions with different energy expenditure (800 or 1,500 kcal) at 70% maximal O2 consumption (Vo2max). Subjects maintained constant energy intake on the day before, the day of, and 2 days after exercise, as verified by dietary recall. Compared with preexercise in either exercise session, there were no differences in plasma leptin concentrations following exercise (0 and 24 hours postexercise) except at 48 hours postexercise, where an approximately 30% decrease (P < .05) was observed. With either duration of exercise, plasma glucose increased about 10% (P < .05), insulin decreased 35% to 46% (P < .05), and cortisol increased 41% to 50% (P < .05, 1,500 kcal only) immediately following exercise, but returned to preexercise values at 24 and 48 hours postexercise. A statistically significant correlation was observed between the changes in leptin and insulin (r = .49, P < .0001). Single exercise sessions of varying energy expenditure decreased the plasma leptin concentration after 48 hours in association with a preceding decrease in insulin.

Effects of four different single exercise sessions on lipids, lipoproteins, and lipoprotein lipase.

The purpose of this study was to determine the threshold of exercise energy expenditure necessary to change blood lipid and lipoprotein concentrations and lipoprotein lipase activity (LPLA) in healthy, trained men. On different days, 11 men (age, 26.7 +/- 6.1 yr; body fat, 11.0 +/- 1.5%) completed four separate, randomly assigned, submaximal treadmill sessions at 70% maximal O2 consumption. During each session 800, 1,100, 1,300, or 1,500 kcal were expended. Compared with immediately before exercise, high-density lipoprotein cholesterol (HDL-C) concentration was significantly elevated 24 h after exercise (P < 0.05) in the 1,100-, 1,300-, and 1,500-kcal sessions. HDL-C concentration was also elevated (P < 0.05) immediately after and 48 h after exercise in the 1,500-kcal session. Compared with values 24 h before exercise, LPLA was significantly greater (P < 0.05) 24 h after exercise in the 1,100-, 1,300-, and 1,500-kcal sessions and remained elevated 48 h after exercise in the 1,500-kcal session. These data indicate that, in healthy, trained men, 1,100 kcal of energy expenditure are necessary to elicit increased HDL-C concentrations. These HDL-C changes coincided with increased LPLA.

Effect of a single session of exercise on lipoprotein(a).

Lipoprotein(a) (Lp(a)) is bound to apolipoprotein B-100 by disulfide linkage and is associated in the upper density range of low density lipoprotein cholesterol. Persons with elevated concentrations of Lp(a) are regarded as having an increased risk for premature coronary artery disease. Although many studies exist evaluating the effects of a single session of exercise on lipids and lipoproteins, little information is available concerning the effects of exercise on Lp(a). Therefore, the purpose of this study was to determine the effects of a single exercise session on plasma Lp(a). Twelve physically active men completed two 30-min submaximal treadmill exercise sessions: low intensity (LI, 50% VO2max) and high intensity (HI, 80% VO2max). Blood samples were obtained immediately before and after exercise. Total cholesterol (LI: before 4.22 +/- 0.26, after 4.24 +/- 0.28; HI: before 4.24 +/- 0.31, after 4.11 +/- 0.28 mmol.l-1, mean +/- SE) and triglyceride (LI: before 1.14 +/- 0.16, after 1.06 +/- 0.16; HI: before 1.12 +/- 0.19, after 1.21 +/- 0.19 mmol.l-1) concentrations did not differ immediately after either exercise session, nor did Lp(a) concentrations differ immediately after either exercise session (LI: before 4.1 +/- 2.2, after 4.0 +/- 2.1: HI: before 3.9 +/- 2.2, after 3.7 +/- 2.0 mg.dl-1). These results suggest that neither a low nor a high intensity exercise session lasting 30 min in duration has an immediate effect on plasma Lp(a).