The influence of age on the control of extracellular fluid homeostasis has been examined in a systematic series of studies over the past 14 years in the Program Project. This present Project (No. 1) expands observations made during this most recent renewal and initiates a new inquiry - the functional cardiovascular, endocrine and renal outcomes of altered extracellular fluid homeostasis. Compelling preliminary data suggest that healthy elderly individuals have high supine morning as well as a clear diurnal pattern of atrial natriuretic peptide, with an acrophase at 2:00 am. Atrial natriuretic peptide levels are highly correlated with noninvasively determined pulmonary capillary wedge pressures. The impact of these diurnal variations in volume regulation on cardiovascular function during exercise and postural change, as well as on nocturnal diuresis will be measured. Young, old, and old-old sedentary and regularly exercising subjects will participate in these studies. The first hypothesis that there is an age-related diurnal variation in cardiac filling pressures (i.e. ANP levels) associated with a blunted cardiovascular response to exercise, postural stress, and an increased nocturnal diuresis. The second hypothesis is that during chronic extravascular volume expansion (achieved by a high sodium diet), healthy elderly display even higher cardiac filling pressures (i.e. ANP levels) with resultant decreases in cardiovascular performance during exercise and postural stress, and an increased nocturnal diuresis. The third hypothesis is that during chronic extravascular volume contraction (achieved by a low sodium diet), the elderly decrease cardiac filling pressures (i.e. ANP levels) resulting in decreased cardiovascular performance during exercise and postural stress, and a decreased nocturnal diuresis. The fourth hypothesis is that habitually exercising healthy elderly subjects show a profile of ANP values, cardiovascular performance, and nocturnal diuresis pattern more like the young group than the sedentary elderly. We hope that this expanded approach to the relationship between fluid volume and cardiovascular, endocrine and renal functional outcomes in the healthy elderly will enhance understanding of the mechanisms responsible for the morbid disorders of extracellular fluid homeostasis in the elderly.
