Physiological and Biochemical Indices of Neurohypophyseal Function in the Aging Fischer Rat

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In order to resolve conflicting reports in the literature on the effect of aging on the hypothalamo neurohypophyseal system (HNS) in rats, multiple parameters associated with the HNS were evaluated in young (4 months), fully mature (14 months), and old (25 months) Fischer 344 rats under basal and stimulated conditions. The hypothalamic hormones oxytocin and vasopressin were compared in radioimmunoassay of serum, urine, brain and pituitary. Information on body weight, water intake, urine output, serum hematocrit and plasma osmolality was also obtained from the same subjects and analyzed together with these data. Finally, semi quantitative histofluorescence assessment of the noradrenergic innervation of the mediobasal hypothalamus from the same animals was performed to determine the extent of central afferent input to the HNS with advancing age. The circulating levels of vasopressin and oxytocin did not significantly differ in the three age groups under basal conditions. Serum vasopressin concentration was increased following water deprivation, and the increase was comparable in all age groups. Serum oxytocin was also increased following water deprivation in all groups, but the increase was greater in the 25-month-old rats relative to the 4-month-old rats. Urinary excretion of vasopressin was used as an index of daily vasopressin secretion. The urinary concentration of vasopressin was less in aged rats relative to young controls, though an increased urine volume in the mature and old animals meant that total vasopressin excretion in the urine was comparable at all ages studied. The increased urine volume in the mature and aged rats does not appear to reflect a decrease in renal sensitivity to vasopressin, since all age groups demonstrated a comparable reduction in urine volume during water deprivation, at comparable concentrations of circulating vasopressin. These data suggest that the increase in urine volume observed in the 14- and 25-month-old rats may be a function of increased fluid intake rather than hyperactivity in the HNS. The concentrations of both peptides were reduced in the posterior pituitary of aged rats, though again, the total amount of peptide in the gland did not change. Only oxytocin showed an age-related change in the hypothalamus, decreasing in the oldest subjects. These data indicate that the ability to secrete adequate quantities of vasopressin in response to dehydration is not compromised in Fisher 344 rats up to 25 months of age.