These proposed studies will investigate the causes of the sex difference in the rate which the kidney ages, since it is known that the female experiences a marked degree of protection from the age dependent deterioration in kidney function compared to the male. Specifically, these experiments will investigate sex differences in the rate at which whole kidney and glomerular hemodynamic changes occur during ageing in the rat and studies will also be conducted to define the mechanism of the proteinuria which develops with age. The renal hemodynamic consequences of several factors which are thought to accelerate kidney ageing will also be examined, specifically the effect of uninephrectomy and high dietary protein intake. The specific hypothesis to be tested here is that a relatively vasodilated kidney early in the life of the male rat and throughout the ageing process renders the kidney susceptible to the occurrence of spontaneous, age-dependent damage, whereas a state of relative vasoconstriction (as occurs in the young, adult female) is protective. Experiments will be performed to investigate whether long-term ovariectomy converts the protected female kidney to more resemble that of the male. Studies will also be carried out to investigate the effect of certain vasoactive hormones on renal and systemic hemodynamics in male and female rats off different ages. These studies will be performed in two strains of rats, the Sprague-Dawley and the Munich-Wistar, comparing young adults (aged 3-4 months), mature adults (aged 10-12 months), ageing rats (aged 18-20 months) and senescent rats (aged 28-30 months). Studies will be conducted using both the chronically catheterized, awake rat preparation and the technique of glomerular micropuncture, carried out under anesthesia.
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