ability did not correlate with the age-related decline in the glomerular filtration rate (GFR) (Dontas et al., 1972; Rowe et al., 1976). While this age-related deficit in water conservation can easily be demonstrated in physiologic studies, it is likely to be of major clinical consequence if individuals are exposed to high solute excretion requirements.
Studies in humans suggest that the concentrating defect is due to an intrarenal defect rather than a failure in the osmotic-induced release of arginine vasopressin (Helderman et al., 1978; Lindeman et al., 1966; Miller and Shock, 1953). Following intravenous infusion of hypertonic saline (3 percent sodium chloride) in eight young (22 to 48 years of age) and eight older (52 to 66 years of age) men, serum arginine vasopressin concentrations rose 4.5 times the baseline in the older men compared with 2.5 times the baseline in the younger men despite similar free water clearances (Helderman et al., 1978). The slope of the serum arginine vasopressin concentration (as a percentage of baseline) versus serum osmolality, an index of the sensitivity of the osmoreceptor, was significantly increased in the older subjects. In addition, intravenous infusion of ethanol in 9 younger (21 to 49 years of age) and 13 older (54 to 92 years of age) men resulted in a progressive decline in plasma arginine vasopressin levels in the young subjects, but failed to have a similar effect in the older subjects (Helderman et al., 1978).
In contrast to osmotic stimulation, volume-pressure-mediated arginine vasopressin release has been found to decrease with old age and appears to be absent in many healthy elderly people (Rowe et al., 1982). An additional factor that may influence arginine vasopressin concentrations and impair water conservation in the elderly is the increase in atrial natriuretic peptide (ANP) concentrations with age, since ANP has been demonstrated to suppress arginine vasopressin release in response to hyperosmolality in young and old individuals (Clark et al., 1991).
Studies in humans reveal an age-related increase in solute excretion and osmolar clearance during dehydration (Rowe et al., 1976). This phenomenon, which may be a reflection of an impaired solute transport by the ascending loop of Henle, may be responsible for the impairment in urine concentrating ability in elderly subjects. This possibility is supported by clearance studies during water diuresis that demonstrate a decrease in the sodium chloride transport in the ascending loop of Henle in elderly subjects (Macias-Nunez et al., 1978, 1980). This defect in solute transport by the thick ascending limb of the loop of Henle could diminish inner medullary hypertonicity and thereby impair urinary concentrating ability.