Decline in renal hemodynamic function in aging SHR: role of androgens.

Abstract

Although men and male rats are at increased risk for age-related renal and cardiovascular disease compared with women and female rats, the mechanisms are unknown. However, castration of male normotensive rats protects against age-related glomerular sclerosis, and castration of spontaneously hypertensive rats (SHR) attenuates the age-related progression of hypertension to levels found in female SHR. The present study was performed to determine whether there are differences between male and female renal function in SHR with aging, and if so, the role that androgens play in the age-related changes in renal function in SHR. Renal hemodynamics, glomerular filtration rate (GFR), and proteinuria were measured in anesthetized male and female SHR aged 7 to 8, 14 to 15, and 30 to 32 weeks (n=5 to 7 per sex per age group). Studies were also performed in male SHR that had been castrated at 4 weeks of age and allowed to age to 7 to 8, 14 to 15, and 30 to 32 months of age (n=5 to 9 per age group). At 7 to 8 weeks of age when blood pressures are similar between male, female, and castrated male SHR, there were no differences in renal hemodynamics between male and female SHR. As the rats aged, mean arterial blood pressure increased in all groups and was higher in the intact male SHR than in females. Blood pressure in aging castrated males was similar to the pressure in aging female SHR. With advancing age, GFR in intact male SHR decreased by 20% to 30% at 14 to 15 and 30 to 32 weeks of age, respectively. Renal plasma flow (RPF) also tended to decrease in male SHR but not statistically so. There was no age-related reduction in GFR or RPF in female or castrated male SHR. With advancing age, renal vascular resistance (RVR) increased in all rats. RVR increased by 40% and 60% at 14 to 15 and 30 to 32 weeks in male SHR. In comparison, RVR increased by 20% and 40% in female SHR at similar ages. RVR in castrated male SHR was similar to RVR in females. The levels of urinary protein excretion increased with aging to 14 weeks in the male SHR, but in females and castrated males urinary protein excretion reached a plateau at 6 to 8 weeks that was maintained until 14 weeks of age and was approximately sixfold lower than in male SHR. These data suggest that androgens may play an important role in mediating the hypertension and the age-related alterations in renal function in the male SHR.