THE EFFECT OF DORSOMEDIAL HYPOTHALAMIC NUCLEUS LESIONS ON KIDNEY-FUNCTION AND STRUCTURE AFTER 1 AND 12 MONTHS

According to the Dillman theory (17), aging results from a deterioration of metabolism that begins with an elevation of hypothalamic receptor thresholds for feedback signals from the periphery. Three hypothalamic areas are known to contain such receptors: the ventromedial and dorsomedial hypothalamic nuclei (DMN) and the lateral hypothalamic area. We have hypothesized that selective destruction of those hypothalamic areas might be followed by physiological changes associated with aging. Electrolytic bilateral DMN lesions were produced in male and female weanling rats. These rats were maintained for up to 13 months of age. Sham-operated rats served as controls. Food intake and body weight were monitored postoperatively and prior to sacrifice. Before sacrifice, tail blood and a 24-h urine samples were obtained. In accordance with previous findings, rats with DMN lesions showed dramatic reductions of ponderal growth and food intake but had normal body composition. Total protein and albumin excretion rates were significantly lower in rats with lesions. The fractional contribution of albumin to total urinary protein was also decreased in rats with lesions. Histological examination of the kidneys showed significantly less pathology in the kidneys of rats with DMN lesions; the severity of renal pathology was correlated directly with proteinuria. These changes were seen as early as 1 month after production of the lesion. The attenuation of age-related changes in kidney function and structure in rats with lesions could be due to reduced food intake (dietary restriction is known to produce similar results), and/or a direct effect of the lesion. The latter could be related to the demonstrated existence in rats with DMN lesions of an altered organismic set point that produces a scaled-down, but otherwise homeostatic normal animal.