Interactions between volume control of body fluid compartments and control of circulation are manifold and intricate. There is a group of physiological mechanisms dealing mainly with the control of volume in the intravascular, extracellular and intracellular compartments, and another group of mechanisms dealing mainly with the short-term, mid-term, and long-term regulation and maintenance of an adequate organ and tissue perfusion under a variety of circumstances. These mechanisms are effective at a molecular, cellular, organ, and system level. Each one of these groups of mechanisms controls a leading variable essential to circulation, i.e. extracellular volume through the regulation of effective intravascular volume, and arterial pressure, respectively. These neurohumoral mechanisms show reciprocal and complex interactions at central level and at effector level which cannot be simply set out as the summation of feed-back loops that control individual variables, but that require a more comprehensive conceptualisation. Perturbation of essential variables triggers responses of varying complexity that depend on the characteristics of the perturbation.
Microgravity affects this complex system. Absence of hydrostatic pressure modifies fluid distribution in the human body and causes alterations in the integrative regulation of pressure and volume. But microgravity also affects other systems, that indirectly impinge upon the integrated control of pressure and volume, notably those that establish spatial references for the body position, and the muscle-skeletal system. Changes in the afferent input profile to the central nervous system are likely to modify the activity of neural substrate of autonomic function and change autonomic outflow during transients. For instance, an alteration in the vestibular-related increase in sympathetic outflow to vessels of the lower limbs when standing up after a space flight may well be a factor that contributes to postflight orthostatism. Changes in the muscle-skeletal system cause changes in the metabolism of calcium and other ions, including sodium, that affect renal regulation of fluid volumes, independently of the changes that might have been induced by fluid translocation, and that may behave competitive with these ones and lead to disbalances and to a lack of a matched control of ions and water.
Thus, weightlessness represents a perturbation of unique value to study human physiology, and the pathophysiology of disuse. It contributes to unmasking pitfalls in established knowledge and to set innovative viewpoints. Human space physiology research has lead to describing a series of phenomena that are not readily explained by existing physiological knowledge, and in some instances even to revise established text-book knowledge.