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AGE-INDUCED RENAL INJURY AND EXPRESSION OF RENAL AMINO ACID TRANSPORTER IN THE SPONTANEOUS HYPERTENSIVE RAT: PP.30.199

Objective: The aim of this study was to investigate whether the effects of aging on the expression of amino acid transporters correlate with impairment of renal function and increases in blood pressure. Design and Methods: 48 h before experiments, 13, 52, and 91 week-old Spontaneous Hypertensive Rats (SHR) and Wistar Kyoto (WKY) rats and were placed in metabolic cages for urine collection. Cardiac puncture was used to collect blood. Sodium quantification was performed by an ion-selective electrode. Analysis of non-fasting plasma creatinine, urinary creatinine and urinary proteins was performed on CobasMiraPlus analyzer. Amino acid transporters expression was determined by western blotting. Results: Tibial length remained constant after maturity. In contrast, kidney weight/tibia length ratio increased 15% and 30% in the older WKY and SHR, respectively. At 13 weeks of age SHR showed a decreased kidney weight/tibia length ratio when compared to age-matched WKY (WKY:0.31 ± 0.01 vs SHR:0.26 ± 0.01). Urinary and fractional excretion of sodium and creatinine clearance did not differ between WKY and SHR at 13 and 52 weeks of age. However, 91 week-old SHR showed significantly decreased in urinary sodium excretion relatively to WKY (WKY:1.9 ± 0.1 vs SHR:1.1 ± 0.2, mg/24 h). Urinary protein excretion was increased in all SHR groups (13wks:25.6 ± 1.6; 52wks:26.4 ± 3.3 and 91wks:41.1 ± 2.7, mg/24 h), but identical between WKY groups (13wks:14.0 ± 0.8; 52wks:13.9 ± 1.2 and 91wks:14.8 ± 1.2, mg/24 h). Renal expression of amino acid transporters LAT1 and LAT2 did not differ between WKY and SHR. Contrasting, in SHR ageing was accompanied by a sustained increase in the expression of both 4F2hc and ASCT2 (4F2hc-13wks and 52wks:15% and 91wks:60%; ASCT2–13wks, 52wks and 91wks:18% increase when compared to age-matched WKY). Conclusions: Aged SHR showed evidences of renal injury, such as increased renal hypertrophy, proteinuria and reduced sodium excretion. These age-related changes in renal function and morphology correlate positively with the increased expression of ASCT2 in the SHR. It is suggested that overexpression of ASCT2 may play a role in the age-related changes in kidney function.