The volume regulating systems are integrated to produce an appropriate response to both acute and chronic volume changes. Their responses include changing the levels of the hormones and neural inputs of the involved systems and/or changing the responsiveness of their target tissues. Weightlessness during space travel produces a volume challenge that is unfamiliar to the organism. Thus, it is likely that these volume regulatory mechanisms may respond inappropriately, e.g., a decrease in total body volume in space and abnormal responses to upright posture and stress on return to Earth. A similar "inappropriateness" also can occur in disease states, e.g., congestive heart failure. While it is clear that weightlessness produces profound changes in sodium and volume homeostasis, the mechanisms responsible for these changes are incompletely understood. Confounding this analysis is sleep deprivation, common in space travel, which can also modify volume homeostatic mechanisms.
The purpose of this project is to provide the required understanding and then to design appropriate countermeasures to reduce or eliminate the adverse effects of microgravity. To accomplish this we are addressing five Specific Aims: 1) To test the hypothesis that microgravity modifies the acute responsiveness of the renin-angiotensin-aldosterone system (RAAS) and renal blood flow; 2) Does simulated microgravity change the circadian rhythm of the volume-regulating hormones?; 3) Does simulated microgravity change the target tissue responsiveness to angiotensin II (AngII)?; 4) Does chronic sleep deprivation modify the circadian rhythm of the RAAS and change the acute responsiveness of this system to posture beyond what a microgravity environment alone does?
Because the renin-angiotensin system (RAS) plays a pivotal role in blood pressure control and volume homeostasis, it likely is a major mediator of the adaptive cardio-renal responses observed during space missions and will be a special focus of this project. Thus, the overall goal of this project is to assess the impact of microgravity and sleep deprivation in humans on volume-regulating systems. To achieve this overall objective, we are evaluating renal blood flow and the status and responsiveness of the volume-regulating systems (RAAS, atrial natriuretic peptide and vasopressin), and the adrenergic system (plasma and urine catecholamines) in both simulated microgravity and normal gravity with and without sleep deprivation. Furthermore, the responses of the volume homeostatic mechanisms to acute stimulation by upright tilt testing, standing and exercise are being evaluated before and after achieving equilibrium with these interventions.
This work has implications for the treatment and prevention of maladaptive hemodynamic responses experienced by astronauts in flight and on return to Earth. It will increase our understanding of the mechanisms by which weightlessness and sleep deprivation change plasma volume and sodium homeostasis, thereby, providing entree to develop appropriate countermeasures.