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 (V̇o_{2 peak}) for 1 h/day for 10 days at 30°C. Before and after ET, thermoregulatory responses were measured during 20-min exercise at pretraining 70% V̇o_{2 peak} in the same environment as during ET under isoosmotic or hyperosmotic conditions. Hyperosmolality by ∼10 mosmol/kgH₂O was attained by acute hypertonic saline infusion. After ET, V̇o_{2 peak} and blood volume (BV) both increased by ∼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 [ΔTH_FVC/ΔP_osmol,°C·(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 ΔTH_FVC/ΔP_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.

Depressive patients often experience difficulty in performing exercise due to physical and psychological barriers. We examined the effects of 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) supplementation during home-based walking training in middle-aged depressive women. Nine outpatients [53 ± 8 (SD) yr] with major depressive disorder participated in the pilot study with randomized, placebo-controlled, double-blind crossover design. They underwent two trials for 7 days, each performing interval walking training (IWT) with ALA + SFC (ALA + SFC) or placebo supplement intake (PLC) intermittently with >a 10-day washout period. For the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. Before and after each trial, subjects underwent a graded cycling test, and lactate concentration in plasma ([Lac⁻]_p), oxygen consumption rate ( $${\dot{{\bf{V}}}{\bf{O}}}_{{\bf{2}}}$$V˙O2 ), and carbon dioxide production rate ( $${\dot{{\bf{V}}}{\bf{\text{CO}}}}_{{\bf{2}}}$$V˙CO2 ) were measured with depression severity by the Montgomery–Åsberg Depression Rating Scale (MADRS). We found that the increases in [Lac⁻]_p, $${\dot{{\bf{V}}}{\bf{O}}}_{{\bf{2}}}$$V˙O2 and $${\dot{{\bf{V}}}{\bf{\text{CO}}}}_{{\bf{2}}}$$V˙CO2 during the test were attenuated only in ALA + SFC ([before vs. after] × workload; all, P < 0.01), accompanied by increased training days, impulse, and time at fast walking during IWT (all, P < 0.05) with decreased MADRS-score (P = 0.001). Thus, ALA + SFC supplementation increased IWT achievement to improve depressive symptoms in middle-aged women.

Muscle atrophy with aging is closely associated with chronic systemic inflammation and lifestyle-related diseases. Here, we assessed whether dried tofu intake during 5-month interval walking training (IWT) enhanced increases in thigh muscle mass and strength and ameliorated susceptibility to inflammation in older women. Subjects (n = 32, ~ 65 years) who performed IWT for > 6 months participated in this study. They were randomly divided into 2 groups: IWT + placebo intake (PLG, n = 16; 108 kcal, 0.2 g protein, 5.5 g fat, and 14.4 g carbohydrate) and IWT + dried tofu intake (DTG, n = 16; 111 kcal, 9.6 g protein, 6.0 g fat, and 4.6 g carbohydrate). They were instructed to repeat ≥ 5 sets of fast and slow walking for 3 min each at ≥ 70 and 40% peak aerobic capacity for walking, respectively, per day for ≥ 4 days/week. Immediately after daily exercise, subjects were instructed to consume the supplements assigned to each group. In the DTG, after IWT, the methylation increased at 4/6 sites in the promoter region of the NFKB2 gene in the whole blood (all, P < 0.04), with an 18% increase in the average methylation of the 6 sites (P = 0.035). On the other hand, in the PLG, the increase occurred at only 2/6 sites, with no significant increase in the average methylation of the 6 sites. No significant differences were observed in increases in thigh muscle strength or cross-sectional area between the groups (all, P > 0.2). Altogether, dried tofu supplementation during IWT likely enhanced the methylation of the NFKB2 gene more than IWT alone, without detectably enhanced increases in thigh muscle strength or cross-sectional area.

• Arterial blood pressure rises at the onset of voluntary locomotion, which is probably advantageous for increasing blood flow to contracting muscles without delay. • We previously reported in free-moving mice that the feedback control of arterial blood pressure through peripheral baroreceptors, which was dominant at rest, was suppressed during activation of the cerebral cortex; however, no neurotransmitter for the mechanisms has been identified. • Central suppression of the feedback control of arterial blood pressure at the onset of voluntary locomotion was abolished in vasopressin V1a receptor-deficient mice and by local infusion of a V1a receptor antagonist into the brainstem area, termed the nucleus tractus solitarii, of control mice. • Thus, central vasopressin might play an important role as a neurotransmitter in the pressor response at the onset of voluntary locomotion. Abstract We previously reported that cerebral activation suppressed baroreflex control of heart rate (HR) at the onset of voluntary locomotion. In the present study, we examined whether vasopressin V1a receptors in the brain were involved in these responses by using free-moving V1a receptor knockout (KO, n= 8), wild-type mice locally infused with a V1a receptor antagonist into the nucleus tractus solitarii (BLK, n= 8) and control mice (CNT, n= 8). Baroreflex sensitivity (ΔHR/ΔMAP) was determined from HR response (ΔHR) to a spontaneous change in mean arterial pressure (ΔMAP) every 4 s during the total resting period, which was ∼8.7 h, of the 12 h measuring period in the three groups. ΔHR/ΔMAP was determined during the periods when the cross-correlation function (R(t)) between ΔHR and ΔMAP was significant (P < 0.05). Cerebral activity was determined from the power density ratio of θ to δ wave band (θ/δ) on the electroencephalogram every 4 s. Spontaneous changes in θ/δ were significantly correlated with R(t) during 62 ± 3% of the total resting period in CNT (P < 0.05), but only 38 ± 4% in KO and 47 ± 2% in BLK (vs. CNT, both P < 0.001). When R(t) and ΔHR/ΔMAP were divided into six bins according to the level of θ/δ, both were positively correlated with θ/δ in CNT (both P < 0.001), while neither was correlated in KO or BLK (all P > 0.05). Moreover, the probability that mice started to move after an increase in θ/δ was 24 ± 4% in KO and 24 ± 6% in BLK, markedly lower than 61 ± 5% in CNT (both P < 0.001), with no suppression of the baroreflex control of HR. Thus, central V1a receptors might play an important role in suppressing baroreflex control of HR during cerebral activation at the onset of voluntary locomotion.

We examined whether a countdown (CD) before voluntary cycling exercise induced prospective vascular adjustment for the exercise and, if so, whether and how muscle sympathetic nerve activity (MSNA) was involved in the responses. Young men performed voluntary cycling in a semi-recumbent position (n=14) while middle cerebral artery blood flow velocity (V_MCA; Doppler ultrasonography), heart rate (HR), arterial pressure (AP; finger photoplethysmography), oxygen consumption rate (VO₂), oxygen saturation in the thigh muscle (StO₂; near-infrared spectrometry), cardiac output (CO; Modelflow method) and total peripheral resistance (TPR) were measured (Exp1). Another group underwent the same exercise protocol but used only the right leg (n=10) while MSNA (microneurography) was measured in the peroneal nerve of the left leg (Exp2). All subjects performed 8 trials with a ≥5-min rest between trials. In 4 trials randomly selected from the 8 trials, exercise onset was signaled by a 30-sec CD, whereas in the remaining 4 trials, exercise was started without CD. We found that CD first increased V_MCA, HR, CO, and mean AP, then decreased TPR and increased StO₂ and VO₂ (Exp1; all, P<0.021). Furthermore, the CD-induced increase in mean AP decreased total MSNA and burst frequency (Exp2; both, P<0.048) through the baroreflex, with decreased TPR and increased StO₂ (Exp2; both, P<0.001). The vasodilation and increased VO₂ continued after the start of exercise. Thus, CD before starting exercise induced the muscle vasodilatory response with a concomitant reduction in MSNA through the baroreflex to accelerate aerobic energy production after the start of exercise.