Renal vasodilatory response to intravenous glycine in the aging rat kidney

Studies were performed in the awake, chronically catheterized male Sprague-Dawley rat to investigate renal hemodynamics in the baseline state and also in response to a large intravenous (IV) amino acid (glycine) load. Studies were performed in young adult rats (age 3 to 4 months), old rats (age 18 months), and senescent rats (age 22 to 24 months). Histologic evaluation of the kidney permitted a correlation between structural and functional changes with aging. Histology showed progressive glomerular damage (sclerosis) with aging. In 18-month-old rats, the glomerular filtration rate (GFR) was normal, which, considering the level of glomerular injury (only 64% normal glomeruli), must indicate heterogeneity of glomerular function, with some hyperfunctioning glomeruli. By 22 to 24 months of age (at which time approximately 50% mortality has occurred in males of this strain), GFR is substantially reduced, as is renal plasma flow rate (RPF). Severe glomerular damage was observed histologically (only 34% normal glomeruli), indicating widespread heterogeneity of glomerular function. Young adult rats displayed a substantial renal vasodilation in response to acute IV glycine infusion, which resulted in approximately 25% increases in GFR and RPF. The renal vascular responsivity to glycine was diminished at 18 months and was completely absent in 22- to 24-month-old rats. This altered renal vasodilatory response to glycine probably reflects both structural changes associated with aging and also the compensatory vasodilation of intact hyperfunctioning remnant nephrons as other nephrons are lost due to aging.