Appropriate and coordinated physiological adjustments continually occur to maintain the body's homeostasis. These activities involve multiple regulatory systems, interacting to preserve their optimal function. While well understood conceptually, few studies have, in fact, examined systematically the interrelationships among different regulatory systems when two or more physiological drives occur simultaneously. As the responses to different drives often utilize the same effector pathways, a potential for conflict is created when these drives are combined and impose concurrent stressful loads on the body, thereby competing for the same mechanisms at the same time. This raises the question: which homeostatic response has priority when competing demands are placed on shared mechanisms? A particular dilemma occurs with regard to body temperature control because the thermoregulatory system does not possess its own effectors, but rather depends on those of other systems, e.g., circulatory, respiratory, etc., which may also be required in the simultaneous defense of other variables. An example of a situation in which such a conflict may arise is when heat exposure, dehydration and infection occur together. These stressors, moreover, call, in part, for opposite responses by common effector mechanisms. Failure to adequately meet the needs could result in decompensation, e.g., dehydration in the heat leads to heat exhaustion. However, under such conditions, catastrophic out-comes usually are averted: compromises are evidently reached that allow the body to cope. The purpose of these proposed experiments, therefore, is to better understand the place of body temperature regulation when it is in competition with other, simultaneous homeostatic systems. We will inject trained, conscious rabbits with pyrogenic doses of an endotoxin, and in one series of experiments, expose them concurrently to various heat loads. In a subsequent series, we will additionally dehydrate the animals for 1 day prior to these treatments. We will analyze the rabbits' responses in terms of the fundamental physiological variable of each regulated system, i.e., for thermoregulation, body temperature; for infection, selected acute-phase reactants; and for dehydration, plasma osmolality. The results should contribute to our understanding of the nature of homeostatic interactions, in the general context of physiological regulation in complex situations.
NIH ExPorter
NIH ExPorter