Bioinformatics Analysis of the Molecular Networks Associated with the Amelioration of Aberrant Gene Expression by a Tyr-Trp Dipeptide in Brains Treated with the Amyloid-ß Peptide.

Short-chain peptides derived from various protein sources have been shown to exhibit diverse bio-modulatory and health-promoting effects in animal experiments and human trials. We recently reported that the oral administration of the Tyr-Trp (YW) dipeptide to mice markedly enhances noradrenaline metabolism in the brain and ameliorates the working-memory deficits induced by the ß-amyloid 25-35 peptide (Aß25-35). In the current study, we performed multiple bioinformatics analyses of microarray data from Aß25-35/YW-treated brains to determine the mechanism underlying the action of YW in the brain and to infer the molecular mechanisms and networks involved in the protective effect of YW in the brain. We found that YW not only reversed inflammation-related responses but also activated various molecular networks involving a transcriptional regulatory system, which is mediated by the CREB binding protein (CBP), EGR-family proteins, ELK1, and PPAR, and the calcium-signaling pathway, oxidative stress tolerance, and an enzyme involved in de novo l-serine synthesis in brains treated with Aß25-35. This study revealed that YW has a neuroprotective effect against Aß25-35 neuropathy, suggesting that YW is a new functional-food-material peptide.

Study on the method to avoid infusion-site adverse events following chemotherapeutic treatment with epirubicin and fosaprepitant using immortalized human umbilical vein endothelial cells.

The combination of intravenous Proemend® containing fosaprepitant meglumine, a prodrug for fosaprepitant (FAP), and Tween 80 and chemotherapy with anthracyclines, such as epirubicin (EPI), can cause infusion-site adverse events in clinical practice. In immortalized human umbilical vein endothelial (HUEhT-1) cells, the cytotoxic effects of FAP, EPI, diluted Proemend with culture medium and Tween 80 alone, and a combination of FAP and EPI, were evaluated using the WST-1 cell viability assay. FAP, EPI and diluted Proemend exhibited cytotoxicity in a concentration-dependent manner and marked synergic cytotoxicity was observed between FAP and EPI. The washing of the cell surface following incubation with diluted Proemend containing FAP and Tween-80 eliminated the synergic cytotoxicity of EPI applied thereafter. These results indicated that washing of the infusion-site vascular tissue following intravenous Proemend administration via intravenous tube flushing with an efficient amount of saline may reduce the infusion-site adverse events, which are caused by the combined use of FAP and EPI.

In Vitro and in Silico Analyses of the Adiponectin Receptor Agonistic Action of Soybean Tripeptides.

The Tyr-Pro (YP) dipeptide can serve as an adiponectin receptor 1 (AdipoR1) agonist. We thus investigated the AdipoR1-agonistic potential of YP-related tripeptides in the soybean protein sequence. Among the 17 soybean candidate tripeptides, those elongated at the C-terminus of YP (0.1 µM YPG, 140 ± 16%; 0.1 µM YPE, 141 ± 22%; 0.1 µM YPP, 145 ± 19%; 0.1 µM YPQ, 143 ± 20%; p < 0.05) significantly promoted glucose uptake by L6 muscle myotubes, comparable to the effect of 0.1 µM AdipoRon (163 ± 52%, p < 0.05). The knockdown of AdipoR1 expression in L6 cells abrogated this effect of YPG and YPP, indicating that the two tripeptides had an AdipoR1 agonistic effect. CHARMM-GUI-aided molecular dynamics simulation in a virtual phospholipid membrane revealed that YPG and YPP were stably positioned at the binding pockets of AdipoR1 (binding free energy < -10 kcal/mol). These findings demonstrate that the tripeptides YPG and YPP, with AdipoR1 agonistic YP sequences, have alternative adiponectin-like potential via their preferential binding to AdipoR1.

SBDS interacts with RNF2 and is degraded through RNF2-dependent ubiquitination.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder caused by mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene that has a variety of clinical features, including exocrine pancreatic insufficiency and hematological dysfunction. The SBDS protein is considered to be involved in ribosome biogenesis, ribosomal RNA metabolism, stabilization of mitotic spindles and cellular stress responses, yet the function of SBDS in detail is still incompletely understood. The multiple functions imply that certain proteins might associate with SBDS and affect its function. In this study, we identified Ring finger protein 2 (RNF2) as a candidate for the SBDS interactor by yeast two-hybrid screening. Moreover, we confirmed the interaction by GST-pull down assay using recombinant proteins and co-immunoprecipitation in HEK293T cells overexpressing RNF2. In addition, it is shown that RNF2 ubiquitinates SBDS and promotes its proteasomal degradation in HEK293T cells. These findings provide new insights into the regulation of SBDS.

Intake of Docosahexaenoic Acid-Enriched Milk Beverage Prevents Age-Related Cognitive Decline and Decreases Serum Bone Resorption Marker Levels.

The pathogenic mechanism of dementia is still unknown, and the fundamental treatment remains to be established. Thus, there is growing interest in preventing dementia through diet. One of the functional ingredients attracting attention is docosahexaenoic acid. We conducted a 12-month, randomized, double-blind, placebo-controlled clinical trial in healthy elderly Japanese individuals with a Mini-Mental State Examination score of 28 or higher at baseline using a docosahexaenoic acid-enriched milk beverage containing 297 mg docosahexaenoic acid and 137 mg eicosapentaenoic acid. Consumption of a docosahexaenoic acid-enriched milk beverage increased the fatty acid levels of docosahexaenoic acid and eicosapentaenoic acid in erythrocyte membranes, which was the primary outcome of this study. Moreover, intake of this beverage prevented age-related cognitive decline and decreased serum bone resorption marker levels. Our data demonstrate that, even at a low dose, long-term daily intake of docosahexaenoic acid prevents dementia and may show beneficial effect on bone health.

Tyr-Trp administration facilitates brain norepinephrine metabolism and ameliorates a short-term memory deficit in a mouse model of Alzheimer's disease.

The physiological actions of orally ingested peptides on the brain remain poorly understood. This study examined the effects of 39 orally administered synthetic Tyr-containing dipeptides on the enhancement of brain norepinephrine metabolism in mice by comparing the concentration of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). Although Tyr-Tyr administration increased blood and cerebral cortex (Cx) Tyr concentrations the most, Tyr-Trp increased Cx MHPG concentration the most. The oral administration of Tyr-Trp ameliorated a short-term memory deficit of a mouse model of cognitive dysfunction induced by amyloid beta peptide 25-35. Gene expression profiling of mouse brain using a microarray indicated that Tyr-Trp administration led to a wide variety of changes in mRNA levels, including the upregulation of genes encoding molecules involved in catecholamine metabolism. A comparative metabolome analysis of the Cx of mice given Tyr-Trp or Tyr-Tyr demonstrated that Tyr-Trp administration yielded higher concentrations of Trp and kynurenine pathway metabolites than Tyr-Tyr administration, as well as higher L-dopa levels, which is the initial product of catecholamine metabolism. Catecholamines were not significantly increased in the Cx of the Tyr-Tyr group compared with the Tyr-Trp group, despite a marked increase in Tyr. Presumably, Tyr-Trp administration enhances catecholamine synthesis and metabolism via the upregulation of genes involved in Tyr and Trp metabolism as well as metabolites of Tyr and Trp. These findings strongly suggest that orally ingested Tyr-Trp modulates the brain metabolome involved in catecholamine metabolism and contributes to higher brain function.

Molecular characterization and expression analysis of a phosphoserine aminotransferase involving l-serine synthesis from silkworm, Bombyx mori.

In this study, we identified and characterized a phosphoserine aminotransferase (bmPSAT) from Bombyx mori (B. mori) that is responsible for l-serine biosynthesis. A complementary DNA that encodes bmPSAT was cloned by reverse transcriptase polymerase reaction and sequenced. The presumed amino acid sequence revealed 47-87% identity with known PSATs from insects, humans, plants, and bacteria. Through phylogenetic analysis, we found that bmPSAT is evolutionary related to insect PSATs. Recombinant bmPSAT was produced in Escherichia coli by using a cold-shock promotor and purified to homogeneity. This enzyme utilizes phosphohydroxypyruvate and glutamate for transamination. bmPSAT messenger RNA (mRNA) was expressed at higher levels in several tissues of standard strain silkworm including the silk gland, whereas a sericin-deficient silkworm strain exhibited a diminished expression of bmPSAT mRNA in the silk gland. These findings indicate that bmPSAT may play an important role in synthesizing and supplying l-serine in the larva of B. mori.

Comprehensive behavioral analysis and quantification of brain free amino acids of C57BL/6J congenic mice carrying the 1473G allele in tryptophan hydroxylase-2.

AIM: Tryptophan hydroxylase 2 (Tph2) is a rate-limiting enzyme for the biosynthesis of 5-hydroxytryptamine (5-HT, serotonin). Previous studies have reported that C1473G polymorphism of the murine Tph2 gene leads to decreased 5-HT levels in the brain and abnormal behavioral phenotypes, such as impaired anxiety- and depression-like behaviors. In this study, to confirm the effect of the C1473G polymorphism on mouse phenotypes, we conducted a comprehensive battery of behavioral tests and measured the amounts of brain free amino acids involved in the production of 5-HT. METHODS: We obtained C57BL/6J congenic mice that were homozygous for the 1473G allele of Tph2 (1473G) and subjected them and their wild-type littermates (1473C) to a battery of behavioral tests. Using reverse-phase high-performance liquid chromatography (HPLC), we measured the amounts of free amino acids in the 5-HT and epinephrine synthetic/metabolic pathways in the frontal cortex, hippocampus, striatum, and midbrain. RESULTS: We failed to detect significant differences between genotypes in depression-like behaviors, anxiety-like behaviors, social behaviors, sensorimotor gaiting, or learning and memory, while 1473G mice exhibited a nominally significant impairment in gait analysis, which failed to reach study-wide significance. In the HPLC analysis, there were no significant differences in the amounts of 5-HT, dopamine, norepinephrine, and epinephrine in the frontal cortex, hippocampus, striatum, and midbrain. CONCLUSION: Our findings do not support the idea that congenic C57BL/6J mice carrying the 1473G allele may represent an animal model of mood disorder under normal conditions without stress.

Comparison of the Effect of Soy and Casein-Derived Peptide Administration on Tyrosine and Catecholamine Metabolism in the Mouse Brain.

The effect of soy and casein peptide intake on the metabolism of amino acids and monoamine neurotransmitters in the serum and brain were examined in C57BL/6 mice. Acute oral administration of soy peptide (0.026 g/30 g body weight) caused a notable increase in tyrosine, a catecholamine precursor, in the serum and cerebral cortex, whereas casein peptide administration at the same dose led to an increase in tyrosine in the serum, but not in the cerebral cortex. In addition to tyrosine, soy peptide administration also led to an effective augmentation of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), a principal metabolite of noradrenaline, and significant facilitation of noradrenergic turnover in the cerebral cortex, brainstem, and hippocampus compared to the vehicle control. Casein peptide administration also led to an increase in MHPG only in the cerebral cortex, and caused facilitation of noradrenergic turnover in the cerebral cortex and brainstem. These in vivo observations suggest that both soy and casein peptide intake at this concentration can lead to an increased availability of tyrosine and stimulation of noradrenergic turnover in the brain.

Early-life Photoperiod Influences Depression-like Behavior, Prepulse Inhibition of the Acoustic Startle Response, and Hippocampal Astrogenesis in Mice.

Environmental factors during early life stages affect behavioral and physiological phenotypes in adulthood. We examined the effect of photoperiods during development on neurogenesis and affective behaviors during adolescence/adulthood using C57BL/6J mice. Mice were born and raised until weaning under long-day conditions (LDs) or short-day conditions (SDs), followed by a 12L12D cycle until adulthood. Adult mice born under SD showed a shorter latency to first immobility in the forced swim test when compared with the mice born under LD. The mice born under SD also exhibited significantly lower prepulse inhibition, which is a characteristic of schizophrenia. However, the mice exposed to SD and LD during the prenatal period only did not show differences in prepulse inhibition. At 4 weeks of age, there were less 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the dentate gyrus (DG) of the hippocampus of mice born under SD when compared with mice born under LD. Double immunostaining showed that the mice born under SD showed less BrdU/glial fibrillary acidic protein (GFAP, an astrocyte marker) cells when compared with mice born under LD. Furthermore, expression of the glucocorticoid receptor in the DG was higher in mice born under SD, and the photoperiod-dependent changes in the number of BrdU-positive cells in the DG were abolished by administration of RU486, a glucocorticoid receptor antagonist. These results suggest that the photoperiod in early life alters astrogenesis in the hippocampus via the hypothalamic-pituitary-adrenal axis and may relate to affective behaviors in adulthood.

Soy peptide ingestion augments the synthesis and metabolism of noradrenaline in the mouse brain.

To examine whether edible peptide intake affects neurotransmitter metabolism in the brain, we evaluated the effect of peptides derived from soy proteins or fish collagen on free amino acids and monoamines in the mouse brain. Ingestion of soy peptides led to markedly higher levels of tyrosine, a catecholamine precursor, in the serum, and cerebral cortex compared to those following ingestion of vehicle alone or collagen peptides. Soy peptide ingestion also effectively increased 3-methoxy-4-hydroxyphenylethyleneglycol and normetanephrine, the principal metabolites of noradrenaline, in the cerebral cortex, hippocampus, and brainstem, whereas collagen peptides did not exert such effects. Further, soy peptide ingestion led to a significant increase in noradrenaline itself in the brainstem, where noradrenergic neurons are present. Noradrenergic turnover was also markedly stimulated in these regions after soy peptide ingestion. These in vivo observations suggest that soy peptide ingestion can maintain and promote the synthesis and metabolism of noradrenaline in the brain.

The Dipeptides Ile-Tyr and Ser-Tyr Exert Distinct Effects on Catecholamine Metabolism in the Mouse Brainstem.

Catecholamine synthesis and transmission in the brain are influenced by the availability of Tyr in the body. In this study, we compared the effects of oral administration of Tyr-containing dipeptides Ile-Tyr, Ser-Tyr, and Tyr-Pro with Tyr alone on catecholamine metabolism in the mouse brainstem. Among these dipeptides, Ile-Tyr administration led to increases in dopamine, the dopamine metabolites homovanillic acid, and 3,4-dihydroxyphenylacetic acid, compared to administration of Ser-Tyr, Tyr-Pro, or Tyr alone. In comparison, administration of Ser-Tyr induced significantly increasing noradrenaline turnover, while Tyr-Pro administration suppressed dopamine turnover. Therefore, oral administration of Ile-Tyr, Ser-Tyr, and Tyr-Pro differentially affected metabolism of dopamine and noradrenaline. These observations strongly suggest that Tyr-containing dipeptides exert distinct effects on catecholamine metabolism in the brainstem when ingested orally.

Orally administrated dipeptide Ser-Tyr efficiently stimulates noradrenergic turnover in the mouse brain.

In this study, we examined the effect of orally administrated dipeptides containing Tyr (Y) on the metabolism of catecholamines in mouse brains. We found that among eight synthetic dipeptides whose sequences are present frequently in soy proteins, Ser-Tyr (SY), Ile-Tyr, and Tyr-Pro had the highest apparent permeability coefficients in monolayers of human intestinal epithelial Caco-2 cells. When administrated orally, SY markedly increased tyrosine content in the cerebral cortex compared to the vehicle control, Ile-Tyr, Tyr-Pro, and Y alone. The oral administration of SY more effectively increased 3-methoxy-4-hydroxyphenylethyleneglycol, the principal metabolite of noradrenaline, in the cerebral cortex and hippocampus than did Ile-Tyr, Tyr-Pro, or Y alone. Central noradrenergic turnover was also markedly stimulated by SY administration. These in vivo observations strongly suggest that SY is more potent in boosting central catecholamine transmission, particularly the noradrenergic system, than Y alone or other dipeptides that include Y.

Impact of intensive high-fat ingestion in the early stage of recovery from exercise training on substrate metabolism during exercise in humans.

Not only increasing body carbohydrate (CHO) stores before exercise but also suppressing CHO oxidation during exercise is important for improving endurance performance. We tested the hypothesis that intensive high-fat ingestion in the early stage of recovery from exercise training (ET) for 2 d would suppress CHO oxidation during exercise by increasing whole body lipolysis and/or fat oxidation. In a randomized crossover design, on days 1 and 2, six male subjects performed cycle ET at 50% peak oxygen consumption (VO(2 peak)) for 60-90 min, and consumed a control diet (CON: 1,224 kcal, 55% carbohydrate, 30% fat) or the same diet supplemented with high fat (HF: 1,974 kcal, 34% carbohydrate, 56% fat) 1 h after ET, with the diet other than post-ET similar in both trials. On day 3, subjects performed cycle exercise at 65% VO(2 peak) until exhaustion. Exercise time to exhaustion was longer in the HF trial than in the CON trial (CON: 48.9 ± 6.7 vs. HF: 55.8 ± 7.7 min, p<0.05). In the HF trial, total fat oxidation until exhaustion was higher, accompanied by higher post-exercise plasma glycerol concentration, than in the CON trial (CON: 213 ± 54 vs. HF: 286 ± 63 kcal, p<0.05), whereas total carbohydrate oxidation until exhaustion was not different between trials. These results suggest that intensive high-fat ingestion in the early stage of recovery from ET for a few days until the day before exercise was an effective means of eliciting a CHO-sparing effect during exercise by enhancing fat metabolism.

[Chordoma which was found as a solitary lung tumor].

We report a rare case of chordoma which was found as a well-circumscribed lesion on chest X-ray films without any symptoms, and removed surgically. According to immunohistochemical examination, it has both of epithelial and mesenchymal cell nature, with characteristically positivestaining of S-100. Therefore, it was diagnosed as a lung metastasis of chordoma. The primary focus was unclear in magnetic resonance imaging (MRI) and the whole body positron emission tomography-computed tomography (PET-CT) inspection. The possibility to be primary lung chordoma can not be denied.

Impact of protein and carbohydrate supplementation on plasma volume expansion and thermoregulatory adaptation by aerobic training in older men.

We examined whether protein-carbohydrate (CHO) supplementation immediately after exercise each day during aerobic training facilitated plasma volume (PV) expansion and thermoregulatory and cardiovascular adaptations in older men. Fourteen moderately active older men [68 +/- 5 (SD) yr] were divided into two groups so as to have no significant differences in anthropometric measures, PV, and peak oxygen consumption rate (Vo(2peak)). Each group was provided with a mixture of protein and CHO (3.2 kcal, 0.18 g protein/kg body wt, Pro-CHO, n = 7) or a non-protein and low-calorie placebo (0.5 kcal, 0 g protein/kg body wt, CNT, n = 7) immediately after cycling exercise (60-75% Vo(2peak), 60 min/day, 3 days/wk) each day for 8 wk at approximately 19 degrees C ambient temperature (T(a)) and approximately 43% relative humidity (RH). Before and after training, we measured PV, cardiac stroke volume (SV), and esophageal temperature (T(es)) during 20-min exercise at 60% of pretraining Vo(2peak) at 30 degrees C T(a) and 50% RH. Moreover, we determined the sensitivity of the chest sweat rate (DeltaSR/DeltaT(es)) and forearm vascular conductance (DeltaFVC/DeltaT(es)) in response to increased T(es) during exercise. After training, PV increased by approximately 6% in Pro-CHO (P < 0.001), with an approximately 10% increase in SV during exercise (P < 0.001), but not in CNT (P > 0.07). DeltaFVC/DeltaT(es) increased by 80% and DeltaSR/DeltaT(es) by 18% in Pro-CHO (both P < 0.01) but not in CNT (P > 0.07). Moreover, we found a significant interactive effect of group x training on PV, SV, and DeltaFVC/DeltaT(es) (all P < 0.02) but with no significant effect of group (P > 0.4), suggesting that the supplement enhanced these responses to aerobic training. Thus postexercise protein-CHO supplementation during training caused PV expansion and facilitated thermoregulatory and cardiovascular adaptations, possibly providing a new training regimen for older men.

Protein and carbohydrate supplementation after exercise increases plasma volume and albumin content in older and young men.

This study examined whether increased plasma volume (PV) and albumin content (Alb(cont)) in plasma for 23 h after exercise were attenuated in older subjects compared with in young adult subjects, and if this attenuation abated by supplementation with protein and carbohydrate (CHO) immediately after exercise. Eight moderately active older (approximately 68 yr) and 8 young (approximately 21 yr) men performed two trials: control (CNT) and Pro-CHO in which subjects consumed placebo (0.5 kcal, 0 g protein, 0.5 mg Na(+) in 3.2 ml total fluid volume/kg body wt) or protein and CHO mixture (3.2 kcal, 0.18 g protein, 0.5 mg Na(+) in 3.2 ml total fluid volume/kg body wt) supplementations, respectively, immediately after high-intensity interval exercise for 72 min [8 sets of 4 min at 70-80% peak oxygen consumption rate (Vo(2peak)) intermitted by 5 min at 20% Vo(2peak)]. PV, Alb(cont), and plasma globulin content (Glb(cont)) were measured before exercise, at the end of exercise, every hour from the 1st to the 5th hour after exercise, and at the 23rd hour after exercise. From 12 h before the start to the end of experiment, food intake was controlled to the age-matched recommended dietary allowances. We found that during the first 4 h after exercise in CNT, Alb(cont) recovered less in the older than the young group by approximately 0.04 g/kg (P < 0.05), while it generally recovered more with Pro-CHO than CNT by approximately 0.09 and approximately 0.04 g/kg in the young and older group, respectively, accompanied by a greater increase in PV by approximately 1 and approximately 2 ml/kg, respectively, during the 23 h after exercise (P < 0.05). Glb(cont) remained constant throughout the experiment in both trials for both age groups. Thus the attenuated responses of Alb(cont) and PV after exercise in older subjects were restored by protein and CHO supplementation immediately after exercise, similarly to young subjects.

Tea catechins enhance the mRNA expression of uncoupling protein 1 in rat brown adipose tissue.

The aim of the present study was to determine whether the antiobesity effects of tea catechins (TCs) are associated with the expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). Male Sprague-Dawley rats were fed a high-fat (HF; 35% fat) diet for 5 weeks, then divided into four groups and fed an HF, HF with 0.5% TC (HFTC), normal-fat (NF; 5% fat) or NF with 0.5% TC (NFTC) diet for 8 weeks. At the end of the experimental period, perirenal and epididymal white adipose tissues (WATs) and interscapular BAT were isolated. The NFTC group had significantly lower perirenal WAT weights than the NF group (NF: 12.7+/-0.53 g; NFTC: 10.2+/-0.43 g; P<.01), but the HF and HFTC groups did not differ significantly. TC intake had no effects on epididymal WAT weights. The NFTC and HFTC groups had significantly lower BAT weights than the NF and HF groups, respectively. The NFTC group had significantly higher UCP1 mRNA levels in BAT than the NF group (NF: 0.35+/-0.02; NFTC: 0.60+/-0.11; P<.05), but the HF and HFTC groups did not differ significantly. Thus, TC intake in the context of the NF diet reduced perirenal WAT weight and up-regulated UCP1 mRNA expression in BAT. These results suggest that the suppressive effect of TC on body fat accumulation is associated with UCP1 expression in BAT.

Acute hypoosmolality attenuates the suppression of cutaneous vasodilation with increased exercise intensity.

We examined the hypothesis that elevation of the body core temperature threshold for forearm skin vasodilation (TH(FVC)) with increased exercise intensity is partially caused by concomitantly increased plasma osmolality (P(osmol)). Eight young male subjects, wearing a body suit perfused with warm water to maintain the mean skin temperature at 34 +/- 1 degree C (ranges), performed 20-min cycle-ergometer exercise at 30% peak aerobic power (VO2(peak)) under isoosmotic conditions (C), and at 65% VO2(peak) under isoosmotic (H(EX)I(OS)) and hypoosmotic (H(EX)L(OS)) conditions. In H(EX)L(OS), hypoosmolality was attained by hypotonic saline infusion with DDAVP, a V2 agonist, before exercise. P(osmol) (mosmol/kg H2O) increased after the start of exercise in both H(EX) trials (P < 0.01) but not in C. The average P(osmol) at 5 and 10 min in H(EX)I(OS) was higher than in C (P < 0.01), whereas that in H(EX)L(OS) was lower than in H(EX)I(OS) (P < 0.01). The change in TH(FVC) was proportional to that in P(osmol) in every subject for three trials. The change in TH(FVC) per unit change in P(osmol) (deltaTH(FVC)/deltaP(osmol), degrees C x mosmol(-1) x kg H2O(-1)) was 0.064 +/- 0.012 when exercise intensity increased from C to H(EX)I(OS), similar to 0.086 +/- 0.020 when P(osmol) decreased from H(EX)I(OS) to H(EX)L(OS) (P > 0.1). Moreover, there were no significant differences in plasma volume, heart rate, mean arterial pressure, and plasma lactate concentration around TH(FVC) between H(EX)I(OS) and H(EX)L(OS) (P > 0.1). Thus the increase in TH(FVC) due to increased exercise intensity was at least partially explained by the concomitantly increased P(osmol).

Ten-day endurance training attenuates the hyperosmotic suppression of cutaneous vasodilation during exercise but not sweating.

It is well known that hyperosmolality suppresses thermoregulatory responses and that plasma osmolality (P(osmol)) increases with exercise intensity. We examined whether the decreased esophageal temperature thresholds for cutaneous vasodilation (TH(FVC)) and sweating (TH(SR)) after 10-day endurance training (ET) are caused by either attenuated increase in P(osmol) at a given exercise intensity or blunted sensitivity of hyperosmotic suppression. Nine young male volunteers exercised on a cycle ergometer at 60% peak oxygen consumption rate (V(O2 peak)) for 1 h/day for 10 days at 30 degrees C. Before and after ET, thermoregulatory responses were measured during 20-min exercise at pretraining 70% V(O2 peak) in the same environment as during ET under isoosmotic or hyperosmotic conditions. Hyperosmolality by approximately 10 mosmol/kgH2O was attained by acute hypertonic saline infusion. After ET, V(O2 peak) and blood volume (BV) both increased by approximately 4% (P < 0.05), followed by a decrease in TH(FVC) (P < 0.05) but not by that in TH(SR). Although there was no significant decrease in P(osmol) at the thresholds after ET, the sensitivity of increase in TH(FVC) at a given increase in P(osmol) [deltaTH(FVC)/deltaP(osmol), degrees C x (mosmol/kgH2O)(-1)], determined by hypertonic infusion, was reduced to 0.021 +/- 0.005 from 0.039 +/- 0.004 before ET (P < 0.05). The individual reductions in deltaTH(FVC)/deltaP(osmol) after ET were highly correlated with their increases in BV around TH(FVC) (r = -0.89, P < 0.005). In contrast, there was no alteration in the sensitivity of the hyperosmotic suppression of sweating after ET. Thus the downward shift of TH(FVC) after ET was partially explained by the blunted sensitivity to hyperosmolality, which occurred in proportion to the increase in BV.