Of all the challenges to the endothelium discussed in the chapters within this volume, perhaps the most extreme is the challenge presented when members of a bipedal species that has evolved exquisite cardiovascular controls to support life on Earth, decides to leave its natural environment to explore a world without gravity. We speak of our pioneering astronauts. This chapter describes the cardiovascular changes that the human body undergoes when it leaves Earth to reside in a zero-gravity (actually microgravity) environment for even short periods of time and discusses how the vascular endothelium (particularly the endothelial nitric oxide synthase [eNOS] enzyme) may participate in the adaptations. We also discuss how other forms of NOS might respond to spaceflight. Results from the ground-based rodent model of microgravity, hindlimb unloading, also will be discussed as they have helped determine mechanisms of cardiovascular adaptations. Finally, we speculate about possible adaptations to spaceflight that have not yet been measured.

When exposed to microgravity, the human body undergoes changes in physiological function that appear to be normal adaptations to the new environment (Table 58-1).The cardiovascular system in particular undergoes profound changes. Unfortunately, these adaptations leave the cardiovascular system ill-equipped to handle a sudden return to the gravity of Earth. The most universal symptom after landing, experienced by virtually every astronaut, is postflight orthostatic intolerance. This manifests at a minimum as an increased heart rate response to upright posture and at a maximum as frank orthostatic hypotension and presyncope (lightheadedness, nausea) or even syncope (fainting). Another universal postflight symptom is decreased exercise capacity after landing. Both of these adverse effects present substantial risks if rapid physical activity or emergency egress is required during or immediately after landing.