Responses of plasma human atrial natriuretic factor to high intensity submaximal exercise in the heat

No data exists regarding responses of human atrial natriuretic factor (ANF) to exercise in the heat. The purpose of this study was to examine the responses of plasma ANF to high intensity submaximal (71% +/- 0.9 VO2max) exercise in the heat over an eight day acclimation period. Fourteen healthy males volunteered to participate in the study. Subjects performed intermittent exercises on a treadmill (0% grade) during 50 min of each 100 min trial in an environmental chamber maintained at 41.2 +/- 0.5 degrees C, 39.0 +/- 1.7% relative humidity. Blood was obtained from an antecubital vein after standing 20 min in the heat prior to exercise, and immediately after exercise. Measures were compared on days 1, 4 and 8. ANF did not change pre- to post-exercise nor did it change over the eight day heat acclimation period despite other heat acclimation adaptations. Conversely, plasma aldosterone (ALDO), renin activity (PRA) and cortisol (COR) all increased (p less than 0.05) pre- to post-exercise on each day but again no changes were observed over the eight day period. These data support that ANF may not increase when ALDO and PRA increases are observed.     

Thermotolerance and heat acclimation may share a common mechanism in humans

Thermotolerance and heat acclimation are key adaptation processes that have been hitherto viewed as separate phenomena. Here, we provide evidence that these processes may share a common basis, as both may potentially be governed by the heat shock response. We evaluated the effects of a heat shock response-inhibitor (quercetin; 2,000 mg/day) on established markers of thermotolerance [gastrointestinal barrier permeability, plasma TNF-α, IL-6, and IL-10 concentrations, and leukocyte heat shock protein 70 (HSP70) content]. Heat acclimation reduced body temperatures, heart rate, and physiological strain during exercise/heat stress) in male subjects (n = 8) completing a 7-day heat acclimation protocol. These same subjects completed an identical protocol under placebo supplementation (placebo). Gastrointestinal barrier permeability and TNF-α were increased on the 1st day of exercise/heat stress in quercetin; no differences in these variables were reported in placebo. Exercise HSP70 responses were increased, and plasma cytokines (IL-6, IL-10) were decreased on the 7th day of heat acclimation in placebo; with concomitant reductions in exercise body temperatures, heart rate, and physiological strain. In contrast, gastrointestinal barrier permeability remained elevated, HSP70 was not increased, and IL-6, IL-10, and exercise body temperatures were not reduced on the 7th day of heat acclimation in quercetin. While exercise heart rate and physiological strain were reduced in quercetin, this occurred later in exercise than with placebo. Consistent with the concept that thermotolerance and heat acclimation are related through the heat shock response, repeated exercise/heat stress increases cytoprotective HSP70 and reduces circulating cytokines, contributing to reductions in cellular and systemic markers of heat strain. Exercising under a heat shock response-inhibitor prevents both cellular and systemic heat adaptations.     

Effect of heat acclimation on heat shock protein 72 and interleukin-10 in humans.

Heat acclimation (HA) results in whole body adaptations that increase heat tolerance, and in addition, HA may also result in protective cellular adaptations. We hypothesized that, after HA, basal intracellular heat shock protein (HSP) 72 and extracellular IL-10 levels would increase, while extracellular HSP72 levels decrease. Ten male and two female subjects completed a 10-day exercise/HA protocol (100-min exercise bout at 56% of maximum O(2) uptake in a 42.5 degrees C DB, 27.9% RH environment); subjects exhibited classic adaptations that accompany HA. Peripheral blood mononuclear cells (PBMCs) were isolated before and after each acclimation session on days 1, 6, and 10; plasma and serum were collected before and after exercise on the 1st and 10th day of HA. SDS-PAGE was used to determine PBMC HSP72 levels during HA, and ELISA was used to measure plasma IL-10 and serum HSP72 concentrations. The increase in PBMC HSP72 from pre- to postexercise on the 1st day of HA was not significant (mean +/- SD, 1.0 +/- 0 vs. 1.6 +/- 0.6 density units). Preexercise HSP72 levels on day 1 were significantly lower compared with the pre- and postexercise samples on days 6 and 10 (mean +/- SD, day 6: 2.1 +/- 1.0 and 2.2 +/- 1.0, day 10: 2.0 +/- 1.3 and 2.2 +/- 1.0 density units, respectively, P < 0.05). There were no differences in plasma IL-10 and serum HSP72 postexercise or after 10 days of HA. The sustained elevation of HSP72 from days 6 to 10 may be evidence of a cellular adaptation to HA that contributes to improved heat tolerance and reduced heat illness risk.     

Exercise-heat acclimation in humans alters baseline levels and ex vivo heat inducibility of HSP72 and HSP90 in peripheral blood mononuclear cells

The induction of cellular acquired thermal tolerance (ATT) during heat acclimation (HA) in humans is not well described. This study determined whether exercise-HA modifies the human heat shock protein (HSP)72 and HSP90 responses and whether changes are correlated with physiological adaptations to HA. Using a 10-day HA protocol comprising daily exercise (treadmill walking) in a hot environment (T(a) = 49 degrees C, 20% RH), we analyzed baseline and ex vivo heat-induced expression of HSP72 and HSP90 in peripheral blood mononuclear cells (PBMCs) isolated prior to exercise from eight subjects on day 1 and 10 of the HA protocol. Classical physiological responses to HA were observed, including significantly reduced heart rate and core body temperature, and significantly increased sweating rate. Baseline levels of HSP72 and HSP90 were significantly increased following acclimation by 17.7 +/- 6.1% and 21.1 +/- 6.5%, respectively. Ex vivo induction of HSP72 in PBMCs exposed to heat shock (43 degrees C) was blunted on day 10 compared with day 1. A correlation was identified (r(2) = 0.89) between changes in core temperature elevation and ex vivo HSP90 responses to heat shock between days 1 and 10, indicating that volunteers demonstrating the greatest physiological HA tended to exhibit the greatest blunting of ex vivo HSP induction in response to heat shock. In summary, 1) exercise-HA resulted in increased baseline levels of HSP72 and HSP90, 2) ex vivo heat inducibility of HSP72 was blunted after HA, and 3) volunteers demonstrating the greatest physiological HA tended to exhibit the greatest blunting of ex vivo HSP induction in response to heat shock. These data demonstrate that physiological adaptations in humans undergoing HA are accompanied by both increases in baseline levels and changes in regulation of cytoprotective HSPs.     

Heat acclimation and physical training adaptations of young women using different contraceptive hormones

Although endogenous and exogenous steroid hormones affect numerous physiological processes, the interactions of reproductive hormones, chronic exercise training, and heat acclimation are unknown. This investigation evaluated the responses and adaptations of 36 inactive females [age 21 +/- 3 (SD) yr] as they undertook a 7- to 8-wk program [heat acclimation and physical training (HAPT)] of indoor heat acclimation (90 min/day, 3 days/wk) and outdoor physical training (3 days/wk) while using either an oral estradiol-progestin contraceptive (ORAL, n = 15), a contraceptive injection of depot medroxyprogesterone acetate (DEPO, n = 7), or no contraceptive (EU-OV, n = 14; control). Standardized physical fitness and exercise-heat tolerance tests (36.5 degrees C, 37% relative humidity), administered before and after HAPT, demonstrated that the three subject groups successfully (P < 0.05) acclimated to heat (i.e., rectal temperature, heart rate) and improved muscular endurance (i.e., sit-ups, push-ups, 4.6-km run time) and body composition characteristics. The stress of HAPT did not disrupt the menstrual cycle length/phase characteristics, ovulation, or plasma hormone concentrations of EU-OV. No between-group differences (P > 0.05) existed for rectal and skin temperatures or metabolic, cardiorespiratory, muscular endurance, or body composition variables. A significant difference post-HAPT in the onset temperature of local sweating, ORAL (37.2 +/- 0.4 degrees C) vs. DEPO (37.7 +/- 0.2 degrees C), suggested that steroid hormones influenced this adaptation. In summary, virtually all adaptations of ORAL and DEPO were similar to EU-OV, suggesting that exogenous reproductive hormones neither enhanced nor impaired the ability of women to complete 7-8 wk of strenuous physical training and heat acclimation.     

The effect of 15 consecutive days of heat–exercise acclimation on heat shock protein 70

The purpose of this study was to investigate the alterations in serum heat shock protein (Hsp) 70 levels during a 15-consecutive-day intermittent heat–exercise protocol in a 29-year-old male ultra marathon runner. Heat acclimation, for the purpose of physical activities in elevated ambient temperatures, has numerous physiological benefits including mechanisms such as improved cardiac output, increased plasma volume and a decreased core temperature (T _c). In addition to the central adaptations, the role of Hsp during heat acclimation has received an increasing amount of attention. The acclimation protocol applied was designed to correspond with the athlete’s tapering period for the 2007 Marathon Des Sables. The subject (VO₂max = 50.7 ml·kg⁻¹·min⁻¹, peak power output [PPO] = 376 W) cycled daily for 90 min at a workload corresponding to 50% of VO₂max in a temperature-controlled room (average WBGT = 31.9 ± 0.9°C). Venous blood was sampled before and after each session for measurement of serum osmolality and serum Hsp70. In addition, T _c, heart rate (HR) and power output (PO) was measured throughout the 90 min to ensure that heat acclimation was achieved during the 15-day period. The results show that the subject was successfully heat acclimated as seen by the lowered HR at rest and during exercise, decreased resting and exercising T _c and an increased PO. The heat exercise resulted in an initial increase in Hsp70 concentrations, known as thermotolerance, and the increase in Hsp70 after exercise was inversely correlated to the resting values of Hsp70 (Spearman’s rank correlation = −0.81, p < 0.01). Furthermore, the 15-day heat–exercise protocol also increased the basal levels of Hsp70, a response different from that of thermotolerance. This is, as far as we are aware, the first report showing Hsp70 levels during consecutive days of intermittent heat exposure giving rise to heat acclimation. In conclusion, a relatively longer heat acclimation protocol is suggested to obtain maximum benefit of heat acclimation inclusive of both cellular and systemic adaptations.     

Opioid peptides modulate production of interferon gamma by human mononuclear cells

The opioid neuropeptides have previously been shown to bind to and affect leukocyte function including lymphocyte proliferation, NK-cell activity, mononuclear cell chemotaxis, immunoglobulin synthesis, and lymphokine production. The effect of the opioid peptides beta-endorphin and Met-enkephalin on interferon gamma (IFN) production by concanavalin A-stimulated human mononuclear cells was examined. Both beta-endorphin and Met-enkephalin enhanced IFN production by the majority of donor mononuclear cells tested and did so at concentrations between 10(-14) and 10(-10) M. When 10(-12) M beta-endorphin or Met-enkephalin were included in concanavalin A-stimulated mononuclear cell cultures, IFN concentrations were significantly enhanced to 205 +/- 45 and 252 +/- 67% of control, respectively. Although the majority of cell preparations tested exhibited an enhanced production of IFN in response to these opioid peptides, some did not. When beta-endorphin or Met-enkephalin were utilized at 10(-11) M, 10 of 15 and 7 of 11 responded with IFN production greater than 20% above the control (untreated) level. There was not an absolute correlation between an enhanced response to beta-endorphin and Met-enkephalin, suggesting the presence of multiple receptor types on these cells for opioids. The opioid receptor antagonist, naloxone, did not significantly prevent the opiate effect. When 10(-8) M naloxone was included in cultures containing 10(-12) M beta-endorphin or Met-enkephalin no significant inhibition of the effect of either opioid on IFN production was observed.     

Response of plasma endorphins, prolactin and catecholamines in women to intense heat in a sauna

Concentrations of immunoreactive beta-endorphin (ir beta-E), corticotropin, cortisol, prolactin and catecholamines in plasma were followed in 11 healthy women during and after exposure to intense heat in a Finnish sauna bath, and compared to those in a similar control situation without exposure to heat. Heat stress significantly increased prolactin and norepinephrine secretion; the percentage increases from the initial plasma concentrations varied from 113 to 1280% (mean 510%) and from 18 to 150% (mean 86%), respectively. The response of the plasma levels of epinephrine, ir beta-E, corticotropin and cortisol to heat exposure was variable. Compared to the control situation, no statistically significant effect of heat exposure on the plasma levels of these hormones was found.     

Met-enkephalin, β-endorphin and cortisol responses to sub-maximal exercise after sleep disturbances

The present study compared the effects of partial sleep deprivation and the effects of an intake of a hypnotic compound (zolpidem) prior to bedtime, on sleep and on hormonal and metabolic adaptations to subsequent exercise. Sleep deprivation consisted of a delayed bedtime and an early getting-up time. Eight young subjects, who slept well and were highly trained athletes, were enrolled in this study. Sleep was recorded polygraphically and the following afternoon exercise was performed on a cycle ergometer for 30 min at 75% of maximal oxygen consumption (VO2max) after a 10-min warm up. Met-enkephalin, beta-endorphin, cortisol, and lactate concentrations were measured at rest and during exercise. The data obtained after experimental sleep, with and without medication were compared with those obtained in the reference condition with normal sleep. Both types of sleep reduction decreased the total sleep time, stage 2 sleep, and rapid eye movement sleep, whereas zolpidem administration did not modify either the duration of sleep or the sleep stages. After the reference night, plasma met-enkephalin did not show any significant change at the end of the submaximal exercise, whereas beta-endorphin, cortisol, and lactic acid concentrations increased significantly in all subjects. The changes in concentration in beta-endorphin were significantly related to the changes in cortisol (r = 0.78; P less than 0.01) and to the changes in plasma lactic acid (r = 0.58; P less than 0.05). Cortisol concentrations were also related to lactic acid values (r = 0.94; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Opioid peptide modulation of circulatory response to hyperventilation in humans

After hyperventilation, systolic blood pressure (SBP) significantly decreased in 10 subjects (group 1), did not change in eight (group 2) and increased in 15 (group 3). Diastolic blood pressure and heart rate increased in all groups. The decrease in SBP was associated with a decrease in plasma catecholamines and increase in beta-endorphin, whereas the increase in SBP was accompanied by an increase in catecholamine and Met-enkephalin levels. Naloxone abolished the hyperventilation-induced SBP and catecholamine decrease only in group 1. These findings show an activation of the endogenous opioid system after hyperventilation and the role of beta-endorphin in reducing SBP in response to the test.     

Morphine, beta-endorphin and [D-Ala2] Met-enkephalin inhibit oxytocin release by acetylcholine and suckling

Morphine inhibits suckling-induced oxytocin (OT) release in lactating mice. Since beta-endorphin and enkephalins have several actions in common with morphine, the action of these opioid peptides on OT release was investigated. In anesthetized lactating rats, OT release was achieved by intraventricular injection of acetylcholine (ACh) or by the physiological stimulus of suckling. The amount of OT released was estimated by comparing milk-ejection responses to these stimuli to those following known amounts of intravenous (IV) OT. Both beta-endorphin and [D-Ala2]Met-enkephalin inhibited ACh-induced and suckling-induced OT release. Naloxone antagonized opiate inhibition in both cases.     

Plasma aldosterone and sweat sodium concentrations after exercise and heat acclimation

This investigation was designed to determine the relationship between the levels of plasma aldosterone and eccrine sweat gland sodium excretion following exercise and heat acclimation. Ten subjects exercised at 45% of their maximal O2 uptake in a hot (40 degrees C), moderately humid (45% relative humidity) environment for 2 h/day on ten consecutive days. Acclimation was verified by significant reductions in exercise heart rate, rectal temperature, and heat storage, as well as significant elevation of resting plasma volume (12%, P less than 0.05) and exercise sweat rate on day 10 compared with day 1 of acclimation. During exercise, the concentration and total content of sodium in sweat as well as plasma aldosterone were significantly decreased from day 1 to day 10. The ratio of sweat sodium reabsorbed to plasma aldosterone concentration was significantly increased from day 1 to day 10 after both 1 and 2 h of exercise. These data indicate that plasma aldosterone concentrations decrease following heat acclimation; and eccrine gland responsiveness to aldosterone, as represented by sweat sodium reabsorption, may be augumented through exercise and heat acclimation.     

The effects of acclimation temperature on pituitary and plasma beta-endorphin in rats at 32.5 degrees C

Endocrine and thermoregulatory responses were studied in male rats exposed to heat (32.5 +/- 0.1 degrees C) from acclimation temperatures of either 24.5 +/- 0.1 degrees C or 29.2 +/- 0.1 degrees C. After 1 hr in the heat, evaporative water loss and tail skin temperature changes in the 24.5 degrees C acclimated rats were greater than in the 29.2 degrees C acclimated rats; both groups displayed similar changes in metabolic rate and rectal temperature. At the respective acclimation temperatures, 29.2 degrees C rats displayed lowered plasma thyroid hormones, elevated beta-endorphin-like immunoreactivity (beta-END-LI) in the plasma, neurointermediate and anterior lobes of the pituitary gland, and no change in plasma corticosterone levels compared to 24.5 degrees C rats. After exposure to 32.5 degrees C for 1 hr, both groups of rats maintained similar plasma corticosterone levels; however, only the 24.5 degrees C group increased plasma thyroxine and beta-END-LI. These data suggest that beta-endorphin may be involved in body temperature regulation during acclimation to elevated environmental temperatures.     

Plasma Met-enkephalin and catecholamine responses to intense exercise in humans.

Native and cryptic Met-enkephalin and catecholamines are coreleased in response to stress. However, it is not known whether Met-enkephalin and catecholamines exhibit concurrent temporal relationships in response to exercise. The purpose of this investigation was to examine the corelease of catecholamines and Met-enkephalin in endurance-trained (n = 6) and untrained (n = 6) male subjects during a 6-min bout of exercise: 4 min at 70% of maximal O2 uptake (VO2max) followed by 2 min at 120% VO2max. Peak catecholamine levels were found at 1 min of recovery. In trained subjects, native Met-enkephalin peaked during exercise at 70% VO2max, declined during exercise at 120% VO2max, and returned to basal levels by 1 min of recovery. In the untrained subjects, native Met-enkephalin peaked at 120% VO2max (6 min) and returned to baseline by 5 min of recovery. In both groups, cryptic Met-enkephalin peaked at 70% VO2max and returned to basal levels during exercise at 120% VO2max. These data demonstrate that during exercise there is a temporal dissociation in plasma levels of Met-enkephalin and catecholamines.     

Plasma levels of beta-endorphin, prolactin and gonadotropins in male athletes after an international nordic ski race

Plasma beta-endorphin, prolactin (PRL), FSH and LH were measured in 17 volunteer male subjects at rest and under the stress caused by a long-distance nordic ski race. The race induced increased levels of beta-endorphin and PRL in all skiers. The changes in PRL with exercise were significantly related to the changes in beta-endorphin (r = 0.69, p less than 0.001). Furthermore, the highly trained skiers training over 150 km.week-1 of nordic ski showed consistently higher post-exercise beta-endorphin and PRL levels than the moderately trained skiers who trained for 20 km.week-1. In addition the race induced slight falls in FSH and LH; however plasma gonadotropin levels did not show any correlation with plasma beta-endorphin concentrations and did not differ between the two groups of skiers. These results suggest that endogenous opioid peptides may modulate PRL secretion in heavy exercise, since they are of minor importance in the release of FSH and LH in such a situation. The observations also suggest that the degree of previous training and the exercise intensity do seem to be responsible for the hormonal changes.     

Skeletal muscle metabolism during exercise is influenced by heat acclimation

The influence of heat acclimation on skeletal muscle metabolism during submaximal exercise was studied in 13 healthy men. The subjects performed 30 min of cycle exercise (70% of individual maximal O2 uptake) in a cool [21 degrees C, 30% relative humidity (rh)] and a hot (49 degrees C, 20% rh) environment before and again after they were heat acclimated. Aerobic metabolic rate was lower (0.1 l X min-1; P less than 0.01) during exercise in the heat compared with the cool both before and after heat acclimation. Muscle and plasma lactate accumulation with exercise was greater (P less than 0.01) in the hot relative to the cool environment both before and after acclimation. Acclimation lowered (P less than 0.01) aerobic metabolic rate as well as muscle and plasma lactate accumulation in both environments. The amount of muscle glycogen utilized during exercise in the hot environment did not differ from that in the cool either before or after acclimation. These findings indicate that accumulation of muscle lactate is increased and aerobic metabolic rate is decreased during exercise in the heat before and after heat acclimation; increased muscle glycogen utilization does not account for the increased muscle lactate accumulation during exercise under extreme heat stress; and heat acclimation lowers the aerobic metabolic rate and muscle and blood lactate accumulation during exercise in a cool as well as a hot environment.     

Beta-endorphin/beta-lipotropin release and gonadotropin secretion after acute exercise in normal males

The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response to acute exercise and the relationship of these opioid peptides to basal and luteinizing hormone-releasing hormone (LRH)-stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion was studied in eight normal male volunteers. Acute exercise resulted in a rise in plasma beta-LPH levels that returned to base line when measured 60 min after exercise. Plasma beta-EP levels did not demonstrate any rise when measured immediately after 20 min of exercise or at 60 min after exercise. Serum LH concentrations in individual volunteers declined to nadir values 60-180 min after exercise after which they showed a rebound to levels higher than the preexercise values in three of five volunteers in whom nadir LH levels were attained before the final (180 min) measurement. Serum FSH concentrations were unaltered by exercise. Acute exercise similarly did not alter the LH/FSH response to exogenous LRH stimulation. Pretreatment of the volunteers with the narcotic antagonist, naloxone, failed to alter the postexercise or LRH-stimulated LH and FSH release. The data suggest that beta-EP does not exert a suppressive effect on LH secretion after acute exercise in normal human males. Whether the suppression of LH secretion after acute exercise in unconditioned males is due to factor(s) cosecreted with beta-LPH, an increase in brain beta-EP or to alternate mechanisms such as alteration in central dopaminergic or GABAergic tone remains to be established.     

Endogenous opioid peptide effects on the guinea-pig biliary tract

The effects of the endogenous opioid peptides, dynorphin (1-13), Met-enkephalin and beta-endorphin, on contraction induced by transmural stimulation of terminal bile duct preparations (terminal cavity and ampulla) and gallbladder were investigated in vitro. These peptides inhibited ampulla contraction, dose dependently. The potency order, indicated by ID50, was the same as in the guinea-pig ileum, but the absolute ID50 values in the ampulla were lower than in the ileum. In the terminal cavity, the dynorphin (1-13) ID50 was still less than in the ampulla, and beta-endorphin and Met-enkephalin did not reduce contraction by as much as 50%. In the gallbladder, the effects of these opioid peptides on contraction induced by transmural stimulation were not significant. The results suggest differences in the receptor populations of the ampulla and terminal cavity, and lack of opiate receptors (at least micro and k receptors) in the gallbladder.     

beta-Endorphin-(1-27) inhibits the spinal beta-endorphin-induced release of Met-enkephalin

The effect of intraventricular beta-endorphin-(1-27) on the spinal release of Met-enkephalin induced by intraventricular beta-endorphin was studied using the intrathecal superfusion technique in urethane anesthetized rats. Intraventricular injection of beta-endorphin at a dose of 15 micrograms released Met-enkephalin from the spinal cord. This release of Met-enkephalin induced by beta-endorphin was significantly reduced by beta-endorphin-(1-27), 60 micrograms, injected intraventricularly. Injection of beta-endorphin (1-27) itself did not cause any release of Met-enkephalin. The finding is in line with the previous report that beta-endorphin (1-27) inhibited the analgesia induced by beta-endorphin.     

Opioid peptide response to spinal cord stimulation in chronic critical limb ischemia

Twelve patients with chronic critical limb ischemia in whom a spinal cord stimulation (SCS) system had been implanted for at least one year had increased microvascular flow and achieved healing of trophic acral lesions. After switching off the system, the clinical improvement persisted for 10 days and the neurohormonal pattern showed high plasma values of beta-endorphin and Met-enkephalin, normal dynorphin B, endothelin-1 and catecholamines, and low nitric oxide. Met-enkephalin levels were further increased (P < 0.01) immediately after switching on the electrical stimulation again. The persistence of high plasma opioid levels after switching off the spinal cord stimulation explains the absence of subjective complaints and suggests an involvement of opioids in the regulation and improvement of the microcirculation.