Increased core body temperature in astronauts during long-duration space missions.

Humans' core body temperature (CBT) is strictly controlled within a narrow range. Various studies dealt with the impact of physical activity, clothing, and environmental factors on CBT regulation under terrestrial conditions. However, the effects of weightlessness on human thermoregulation are not well understood. Specifically, studies, investigating the effects of long-duration spaceflight on CBT at rest and during exercise are clearly lacking. We here show that during exercise CBT rises higher and faster in space than on Earth. Moreover, we observed for the first time a sustained increased astronauts' CBT also under resting conditions. This increase of about 1 °C developed gradually over 2.5 months and was associated with augmented concentrations of interleukin-1 receptor antagonist, a key anti-inflammatory protein. Since even minor increases in CBT can impair physical and cognitive performance, both findings have a considerable impact on astronauts' health and well-being during future long-term spaceflights. Moreover, our findings also pinpoint crucial physiological challenges for spacefaring civilizations, and raise questions about the assumption of a thermoregulatory set point in humans, and our evolutionary ability to adapt to climate changes on Earth.

Erythropoietin as a volume-regulating hormone: an integrated view.

The intravascular volume consists of 40% to 45% red cells. Their production is controlled predominantly by erythropoietin (EPO), a hormone that is secreted particularly when tissue hypoxia is present. Because of this high percentage of the total intravascular volume the question comes to mind that, in addition to hypoxia, can volume-regulation mechanisms, known to be responsible for the maintenance of plasma volume, modulate EPO secretion when the total vascular volume changes? Indeed, there is evidence that in situations in which the intravascular volume or specifically the intrathoracic volume is altered, EPO secretion is affected. EPO secretion increases when the intrathoracic volume decreases 24 hours after water immersion or after endurance exercise when a negative water balance prevails. A head-down tilt on the other side induces central engorgement leading to a decrease of EPO concentrations. Under these experimental conditions no hypoxia was seen, supporting the idea that a volume stimulus outgoing from intrathoracic parts of the circulation modulated EPO secretion. Further observations from the clinical side are needed to support these ideas and the consequences need to be implemented into clinical practice.

Anemia and erythropoietin in space flights.

Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at -6 degrees , water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights.

Hypertension, sodium retention, calcium excretion and osteopenia in Dahl rats.

BACKGROUND: Salt-sensitive hypertension in the Dahl rat is associated with abnormalities in both calcium (Ca2+) and sodium (Na) homeostasis. OBJECTIVE: To test the hypothesis that salt-induced abnormal Ca(2+) handling in Dahl salt-sensitive (DSS) rats is associated with negative Ca(2+) balance and bone disease. METHODS: Ca(2+) excretion in acute and chronic Na(+) loading and electrolyte and water balance were determined by balance studies in Dahl salt-resistant (DSR) and salt-sensitive (DSS) rats fed 8 or 0.1% NaCl for 4 weeks. A dry ashing procedure was used to determine Na(+), Ca(2+), and water content and their association with blood pressure in the rats. RESULTS: When fed 8% NaCl, DSS rats initially maintained a positive Ca(2+) balance and showed decreased natriuresis compared with DSR rats. During the course of Na(+) loading, DSS rats increased natriuresis and calciuresis. After 4 weeks of salt loading, cumulative Na balance was greater and cumulative Ca(2+) balance was less in DSS than in DSR rats. In addition, DSS rats developed osteopenia. Bone mineral content correlated inversely with blood pressure in DSS rats. Acute saline volume expansion in DSS rats demonstrated their ability to excrete the Na load fully, but led to an exaggerated renal loss of Ca(2+) compared with DSR rats. CONCLUSION: DSS, but not DSR, develop Ca(2+) loss and ostopenia during chronic Na(+) loading. We speculate that Na retention in DSS rats fed a high Na diet may be in part a compensatory mechanism to maintain Ca(2+) balance.

Osmotically inactive skin Na+ storage in rats.

Compared with age-matched men, women are resistant to the hypertensive effects of dietary NaCl; however, after menopause, the incidence of salt-sensitive hypertension is similar in women and men. We recently suggested that osmotically inactive Na+ storage contributes to the development of salt-sensitive hypertension. The connective tissues, including those immediately below the skin that may serve as a reservoir for osmotically inactive Na+ storage, are affected by menopause. We tested the hypothesis that ovariectomy (OVX) might reduce osmotically inactive Na+ storage capacity in the body, particularly in the skin. Male, female-fertile, and female OVX Sprague-Dawley (SD) rats were fed a high (8%)- or low (0.1%)-NaCl diet. The groups received the diet for 4 or 8 wk. At the end of the experiment, subgroups received 0.9% saline infusion and urinary Na+ and K+ excretion was measured. Wet and dry weight (DW), water content in the body and skin, total body Na+ (rTBNa+) and skin Na+ (rSKNa+) content were measured relative to DW by desiccation and dry ashing. There were no gender differences in osmotically inactive Na+ storage in SD rats. All SD rats accumulated Na+ if fed 8% NaCl, but rTBNa+ was lower in OVX rats than in fertile rats on a low (P < 0.001)- and a high (P < 0.05)-salt diet. OVX decreased rSKNa+ (P < 0.01) in the rats. A high-salt diet led to Na+ accumulation (DeltaSKNa+) in the skin in all SD rats. Osmotically inactive skin Na+ accumulation was approximately 66% of DeltaSKNa+ in female and 82% in male-fertile rats, but there was no osmotically inactive Na+ accumulation in OVX rats fed 8% NaCl. We conclude that skin is an osmotically inactive Na+ reservoir that accumulates Na+ when dietary NaCl is excessive. OVX leads to an acquired reduction of osmotically inactive Na+ storage in SD rats that predisposes the rats to volume excess despite a reduced Na+ content relative to body weight.

Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model.

Recent evidence suggested that Na can be stored in an osmotically inactive form. We investigated whether osmotically inactive Na storage is reduced in a rat model of salt-sensitive (SS) hypertension. SS and salt-resistant (SR) Dahl-Rapp rats as well as Sprague-Dawley (SD) rats were fed a high (8%)- or low (0.1%)-NaCl diet for 4 wk (n = 10/group). Mean arterial pressure (MAP) was measured at the end of the experiment. Wet and dry weights, water content, total body Na (TBS), and bone Na content were measured by dessication and dry ashing. MAP was higher in both Dahl strains than in SD rats. In SS rats, 8% NaCl led to Na accumulation, water retention, and hypertension due to impaired renal Na excretion. There was no dietary-induced Na retention in SR and SD rats. TBS was variable; nevertheless, TBS was significantly correlated with body water and MAP in all strains. However, the extent of Na-associated volume and MAP increases was strain specific. Osmotically inactive Na in SD rats was threefold higher than in SS and SR rats. Both SS and SR Dahl rat strains displayed reduced osmotically inactive Na storage capacity compared with SD controls. A predisposition to fluid accumulation and high blood pressure results from this alteration. Additional factors, including impaired renal Na excretion, probably contribute to hypertension in SS rats. Our results draw attention to the role of osmotically inactive Na storage.