SUMMARY1. Heat acclimation was induced in eight subjects by asking them to exercise until exhaustion at 60 % of maximum oxygen consumption rate (VO ) for 9-12 consecutive days at an ambient temperature of 40°C, with 10% relative humidity (RH). Five control subjects exercised similarly in a cool environment, 20 0C, for 90 min for 9-12 days; of these, three were exposed to exercise at 40°C on the first and last day.2. Acclimation had occurred as seen by the increased average endurance from 48 min to 80 min, the lower rate of rise in the heart rate (HR) and core temperature and the increased sweating.3. Cardiac output increased significantly from the first to the final heat exposure from 19 6 to 21V4 1 min-1; this was possibly due to an increased plasma volumne and stroke volume. 4. The mechanism for the increased plasma volume may be an isosmotic volume expansion caused by influx of protein to the vascular compartment, and a sodium retention induced by a significant increase in aldosterone.5. The exhaustion coincided with, or was elicited when, core temperature reached 39-7 + 0 15°C; with progressing acclimation processes it took progressively longer to reach this level. However, at this point we found no reduction in cardiac output, muscle (leg) blood flow, no changes in substrate utilization or availability, and no recognized accumulated 'fatigue' substances.6. It is concluded that the high core temperature per se, and not circulatory failure, is the critical factor for the exhaustion during exercise in heat stress.

Acute and repeated exposure for 8-13 consecutive days to exercise in humid heat was studied. Twelve fit subjects exercised at 150 W [45% of maximum O2 uptake (V.O2,max)] in ambient conditions of 35 degrees C and 87% relative humidity which resulted in exhaustion after 45 min. Average core temperature reached 39.9 +/- 0.1 degrees C, mean skin temperature (T-sk) was 37.9 +/- 0.1 degrees C and heart rate (HR) 152 +/- 6 beats min-1 at this stage. No effect of the increasing core temperature was seen on cardiac output and leg blood flow (LBF) during acute heat stress. LBF was 5.2 +/- 0.3 l min-1 at 10 min and 5.3 +/- 0.4 l min-1 at exhaustion (n = 6). After acclimation the subjects reached exhaustion after 52 min with a core temperature of 39.9 +/- 0.1 degrees C, T-sk 37.7 +/- 0.2 degrees C, HR 146 +/- 4 beats min-1. Acclimation induced physiological adaptations, as shown by an increased resting plasma volume (3918 +/- 168 to 4256 +/- 270 ml), the lower exercise heart rate at exhaustion, a 26% increase in sweating rate, lower sweat sodium concentration and a 6% reduction in exercise V.O2. Neither in acute exposure nor after acclimation did the rise of core temperature to near 40 degrees C affect metabolism and substrate utilization. The physiological adaptations were similar to those induced by dry heat acclimation. However, in humid heat the effect of acclimation on performance was small due to physical limitations for evaporative heat loss.

Erythropoietin (Epo) has been suggested to affect plasma volume, and would thereby possess a mechanism apart from erythropoiesis to increase arterial oxygen content. This, and potential underlying mechanisms, were tested in eight healthy subjects receiving 5000 IU recombinant human Epo (rHuEpo) for 15 weeks at a dose frequency aimed to increase and maintain haematocrit at approximately 50%. Red blood cell volume was increased from 2933 ± 402 ml before rHuEpo treatment to 3210 ± 356 (P < 0.01), 3117 ± 554 (P < 0.05), and 3172 ± 561 ml (P < 0.01) after 5, 11 and 13 weeks, respectively. This was accompanied by a decrease in plasma volume from 3645 ± 538 ml before rHuEpo treatment to 3267 ± 333 (P < 0.01), 3119 ± 499 (P < 0.05), and 3323 ± 521 ml (P < 0.01) after 5, 11 and 13 weeks, respectively. Concomitantly, plasma renin activity and aldosterone concentration were reduced. This maintained blood volume relatively unchanged, with a slight transient decrease at week 11, such that blood volume was 6578 ± 839 ml before rHuEpo treatment, and 6477 ± 573 (NS), 6236 ± 908 (P < 0.05), and 6495 ± 935 ml (NS), after 5, 11 and 13 weeks of treatment. We conclude that Epo treatment in healthy humans induces an elevation in haemoglobin concentration by two mechanisms: (i) an increase in red cell volume; and (ii) a decrease in plasma volume, which is probably mediated by a downregulation of the rennin-angiotensin-aldosterone axis. Since the relative contribution of plasma volume changes to the increments in arterial oxygen content was between 37.9 and 53.9% during the study period, this mechanism seems as important for increasing arterial oxygen content as the well-known erythropoietic effect of Epo.

Circulatory changes and arterial plasma hormone concentrations were measured in seven healthy young adults during 30 and 60 degrees passive head-up tilt with the subjects supported by a saddle. The 30 degrees tilt induced a decrease in pulse pressure (Pp) from 45 +/- 2 to 35 +/- 4 (mean +/- SE) mmHg concomitant with an increase in heart rate (HR) from 58 +/- 4 to 78 +/- 8 beats/min and a marginal increase in mean arterial pressure (MAP). Norepinephrine increased from 180 +/- 20 to 310 +/- 40 pg/ml, aldosterone increased fivefold, and angiotensin II increased from 8 +/- 2 to 22 +/- 7 pg/ml. The 60 degrees tilt initially produced changes, which were qualitatively similar to the 30 degrees tilt. However, after 19 +/- 3 min sudden decreases were seen in MAP (94 +/- 3 to 50 +/- 8 mmHg), in Pp (38 +/- 5 to 18 +/- 4 mmHg), and in HR (90 +/- 7 to 57 +/- 6 beats/min). Concomitantly, epinephrine doubled while norepinephrine remained unchanged; the vagally controlled hormone pancreatic polypeptide increased from 29 +/- 3 to 51 +/- 8 pmol/l, vasopressin from 4 +/- 1 to 126 +/- 58 pg/ml, and angiotensin II from 23 +/- 9 to 35 +/- 12 pg/ml. The hypotensive bradycardiac episode was immediately reversible on termination of the head-up tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated whether a reduction in cardiac output during dynamic exercise results in vasoconstriction of active skeletal muscle vasculature. Nine subjects performed four 8-min bouts of cycling exercise at 71 +/- 12 to 145 +/- 13 W (40-84% maximal oxygen uptake). Exercise was repeated after cardioselective (beta 1) adrenergic blockade (0.2 mg/kg metoprolol iv). Leg blood flow and cardiac output were determined with bolus injections of indocyanine green. Femoral arterial and venous pressures were monitored for measurement of heart rate, mean arterial pressure, and calculation of systemic and leg vascular conductance. Leg norepinephrine spillover was used as an index of regional sympathetic activity. During control, the highest heart rate and cardiac output were 171 +/- 3 beats/min and 18.9 +/- 0.9 l/min, respectively. beta 1-Blockade reduced these values to 147 +/- 6 beats/min and 15.3 +/- 0.9 l/min, respectively (P < 0.001). Mean arterial pressure was lower than control during light exercise with beta 1-blockade but did not differ from control with greater exercise intensities. At the highest work rate in the control condition, leg blood flow and vascular conductance were 5.4 +/- 0.3 l/min and 5.2 +/- 0.3 cl.min-1.mmHg-1, respectively, and were reduced during beta 1-blockade to 4.8 +/- 0.4 l/min (P < 0.01) and 4.6 +/- 0.4 cl.min-1.mmHg-1 (P < 0.05). During the same exercise condition leg norepinephrine spillover increased from a control value of 2.64 +/- 1.16 to 5.62 +/- 2.13 nM/min with beta 1-blockade (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Serotonin (5-HT), 5-HT agonists, the 5-HT precursor 5-hydroxytryptophan, 5-HT-releasers and -reuptake inhibitors stimulate the release of vasopressin and oxytocin. We investigated the involvement of 5-HT receptors in the serotonergic regulation of vasopressin and oxytocin secretion. Vasopressin and oxytocin secretion was stimulated by 5-HT, the 5-HT(1A+1B+5A+7) agonist 5-carboxamidotryptamine (5-CT), the 5-HT(2A+2C) agonist DOI, the 5-HT(2C+2A) agonist mCPP, the 5-HT(2C) agonist MK-212, the 5-HT(3) agonist SR 57277 and the 5-HT(4) agonist RS 67506. The 5-HT(1A) agonist 8-OH-DPAT, which had no effect on vasopressin secretion, stimulated oxytocin secretion. The 5-HT-induced release of vasopressin and oxytocin was inhibited by central infusion of the 5-HT antagonists WAY 100635 (5-HT(1A)), LY 53857 (5-HT(2A+2C)), ICS 205-930 (5-HT(3+4)) and RS 23597 (5-HT(4)). The 5-HT2+6+7 antagonist metergoline in combination with the 5-HT1A+2+7 antagonist methysergide inhibited the stimulatory effect of 5-CT on both hormones, whereas the 5-HT1A+1B antagonist cyanopindolol only inhibited the oxytocin response. The 5-HT(2A) antagonist 4-(4-flourobenzoyl)-1-(4-phenylbutyl)-piperidine oxalate had no effect on DOI-induced hormone response. The 5-HT(2C) antagonist Y 25130 partly inhibited the stimulating effect of MK-212. ICS 205-930 and RS 23597 inhibited vasopressin and oxytocin secretion induced by RS 67506. WAY 100635 inhibited 8-OH-DPAT-induced oxytocin secretion. We conclude that 5-HT-induced vasopressin secretion primarily is mediated via 5-HT(2C), 5-HT(4) and 5-HT(7) receptors, whereas 5-HT(2A), 5-HT(3) and 5-HT(5A) receptors seem to be of minor importance. 5-HT-induced oxytocin secretion involves 5-HT(1A), 5-HT(2C) and 5-HT(4) receptors; in addition an involvement of 5-HT(1B), 5-HT(5A) and 5-HT(7) receptors seems likely, whereas 5-HT(2A) and 5-HT(3) receptors seem to be less important.

To evaluate whether electrical admittance of intracellular water is applicable for monitoring filling of the heart, we determined the difference in intracellular water in the thorax (Thorax(ICW)), measured as the reciprocal value of the electrical impedance for the thorax at 1.5 and 100 kHz during lower body negative pressure (LBNP) in humans. Changes in Thorax(ICW) were compared with positron emission tomography-determined C(15)O-labeled erythrocytes over the heart. During -40 mmHg LBNP, the blood volume of the heart decreased by 21 +/- 3% as the erythrocyte volume was reduced by 20 +/- 2% and the plasma volume declined by 26 +/- 2% (P < 0.01; n = 8). Over the heart region, LBNP was also associated with a decrease in the technetium-labeled erythrocyte activity by 26 +/- 4% and, conversely, an increase over the lower leg by 92 +/- 5% (P < 0.01; n = 6). For 15 subjects, LBNP increased thoracic impedance by 3.3 +/- 0.3 Omega (1.5 kHz) and 3.0 +/- 0.4 Omega (100 kHz), whereas leg impedance decreased by 9.0 +/- 3.3 Omega (1.5 kHz) and 6.1 +/- 3 Omega (100 kHz; P < 0.01). Thorax(ICW) was reduced by 7.1 +/- 1.9 S. 10(-4) (P < 0.01) and intracellular water in the leg tended to increase (from 37.8 +/- 4.6 to 40.9 +/- 5.0 S. 10(-4); P = 0.08). The correlation between Thorax(ICW) and heart erythrocyte volume was 0.84 (P < 0.05). The results suggest that thoracic electrical admittance of intracellular water can be applied to evaluate changes in blood volume of the heart during LBNP in humans.

It was the purpose of this study to investigate how the endocrine and renal mechanisms of fluid volume control in humans (n = 4) adapt to microgravity by applying an intravenous isotonic saline infusion. The acute ground-based supine (Sup) and seated (Seat) positions were chosen as references. During microgravity, renal sodium excretion (UNaV) was doubled during the second and third hours after infusion compared with during Seat (P < 0.05) but blunted during the first hour after infusion compared with during Sup, leading to a reduction in cumulative UNaV (59 +/- 15 vs. 108 +/- 12 mmol/5 h; P < 0.05). Plasma norepinephrine (NE) attained the highest value 3 h after infusion during microgravity (31 +/- 5 x 10(-2) ng/ml vs. 19 +/- 1 and 13 +/- 3 x 10(-2) ng/ml for Seat and Sup, respectively; P < 0.05). Inflight levels of plasma renin and aldosterone were very similar to levels during Seat. In conclusion, 1) the microgravity-adapted renal responses to infusion reflected a condition in between that of ground-based Seat and Sup, respectively, and 2) the plasma levels of NE, renin, and aldosterone were elevated inflight and not related to the changes in UNaV and urinary flow rate. These observations are in contrast to results of ground-based simulation experiments and might partly have been caused by a prior inflight reduction in extracellular fluid volume. The high levels of NE during microgravity warrant further investigation.