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1 Human Adaptation and Countermeasures Office, Wyle Laboratories, Houston, TX, USA
2 Division of Space Life Sciences, Universities Space Research Association, Houston, TX, USA
3 Astronaut Office, NASA Johnson Space Center, Houston, TX, USA
4 Human Adaptation and Countermeasures Office, NASA Johnson Space Center, Houston, TX, USA
* To whom correspondence should be addressed. E-mail: wwaters{at}ems.jsc.nasa.gov.
Head-down bedrest changes the values of many cardiovascular and endocrine variables and also elicits significant hypovolemia. Because previous studies had not controlled for hypovolemia, it is unknown if the reported changes were primary effects of bedrest, or were secondary effects of bedrest-induced hypovolemia. Accordingly, we hypothesized that restoring plasma volume with salt tablets and water after 12 days of head-down bedrest would result in an absence of hemodynamic and endocrine changes and a reduced incidence of orthostatic hypotension. In 10 men, we measured pre- to post-bedrest changes in venous and arterial pressures; heart rate; stroke volume; cardiac output; vascular resistance; plasma norepinephrine, epinephrine, vasopressin, renin activity (PRA), and aldosterone responses to different tilt levels (0°, -10°, 20°, 30°, and 70°); and plasma volume and platelet 
2- and lymphocyte 
2-adrenoreceptor densities/affinities (0° only). Fluid loading at the end of bedrest restored plasma volume and resulted in the absence of post-bedrest orthostatic hypotension and changes in supine hemodynamic and endocrine variables. Fluid loading did not prevent post-bedrest increases in 2-adrenoreceptor density or decreases in the aldosterone/PRA ratio (P=0.05, for each). Furthermore, post-bedrest heart rate, epinephrine, and PRA responses to upright tilt were increased (P<0.05) despite the fluid load. These results suggest that incidents of orthostatic hypotension and many of the changes in supine hemodynamic and endocrine variables in volume-depleted bedrested subjects occur secondarily to the hypovolemia. Despite normovolemia post-bedrest, 2-adrenoreceptors were upregulated and heart rate, epinephrine, and PRA responses to tilt were augmented, indicating that those changes are independent of volume depletion.
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