POTENTIAL ADAPTATIONS TO ACUTE-HYPOXIA - HCT, STRESS PROTEINS, AND SET-POINT FOR TEMPERATURE REGULATION

Severe, intermittent hypoxia (hypoxic conditioning, HC) increases surv ival time during subsequent lethal hypoxia in mice. This protective ef fect was blocked by naloxone, suggesting an opioid-dependent mechanism . We proposed and evaluated three potential mechanisms of this acute a daptation: I)increased hematocrit (Her), 2) protein synthesis, and 3) decreased set point for temperature regulation (set point). Increased hematocrit is a well-studied adaptation to chronic hypoxia and. could be acutely initiated by sympathetically mediated splenic contraction. Survival during stress can be prolonged by synthesis of stress protein s. We tested this hypothesis using two protein synthesis inhibitors, a nisomycin and cycloheximide. Our third hypothesis is that set point is decreased after HC. e regulated decrease in body temperature would lo wer oxygen demand during hypoxia. Our studies indicate that hematocrit and protein synthesis are not dominant mechanisms of acute adaptation to hypoxia. However, we have observed a naloxone blockable decrease i n set point after HC, supporting a mechanism in which acute adaptation involves an endogenous opioid-dependent decrease in set point. These studies also demonstrate that set point could be a more dominant contr ibutor than body temperature to hypoxic tolerance.