Impaired urinary L-dopa/dopamine ratio as an early predictor of renal damage in fructose overloaded hypertensive rats

PUYO AM; KRAVETZ MC; RUKAVINA MIKUSIC NL; KOUYOUMDZIAN NM; LEE HJ; DEL MAURO J; PANDOLFO M; HOCHT C; GORZALCZANY S; PEREDO H; FERNÁNDEZ BE; CHOI MR

Atenas

Congreso; Joint Meeting ESH-ISH Hypertension; 2014

European Society of Hypertension

Fructose overload produces in the rat metabolic changes, insulin resistance, hypertension and kidney damage. We hypothesize that these changes are associated with alterations in the renal dopaminergic system contributing to sodium retention and hypertension, preceding urinary microalbuminuria, then changes in the renal production of dopamine (DA) were evaluated through the urinary L-DOPA/DA ratio and its relationship with the evolution of natriuresis, systolic blood pressure (SBP) and microalbuminuria in male Sprague Dawley rats. The groups studied were: a) Control (C, tap water to drink) and b) Fructose overloaded: (F, 10% w/v of fructose to drink),treated during 4 (C4,F4), 8 (C8,F8) and 12 (C12,F12) weeks, respectively (n=8 rats per group and per period). L-DOPA and DA were determined by HPLC; diuresis, sodium and creatinine were measured in 24 hr. urine samples; and creatinine, triglycerides, glucose and insulin in plasma. SBP was determined by tail-cuff. Fructose overload increased SBP (mmHg, C4: 121±8 vs F4: 145±1*; C8: 130±4 vs F8: 161±10#; C12: 133±5 vs F12: 163±4#), triglyceridemia (mg/dl, C8: 44±8 vs. F8: 116±10#; C12: 57±20 vs. F12: 143±18#), insulinemia (ng/ml, C8: 1.18±0.13 vs. F8: 3.05±0.75*; C12: 1.03±0.18 vs. F12: 1.9±0.31*), L-DOPA/DA ratio (C4: 0.49±0.05 vs F4: 1.9±0.09#; C8: 0.53±0.06 vs F8: 2.35±0.1#; C12: 0.54±0.07 vs F12: 2.57±0.2#), urine output (ml/24 hrs, C4: 11.79±1.42 vs F4: 24.54±2.05#; C8: 9.98±1.01 vs F8: 23.52±1.9#; C12: 11.55±1.6 vs F12: 28.37±2.07#), glycemia (mg/dl, C8: 144±12 vs. F8: 175±11*; C12: 135±6 vs. F12: 157±15) and decreased urinary sodium excretion (mEq/24 hr, C4: 1.01±0.05 vs F4: 0.83±0.04*; C8: 1.02±0.08 vs F8: 0.72±0.05#; C12: 1.04±0.08 vs F12: 0.64±0.04#) *p<0.05, #p<0.01. Fructose-induced microalbuminuria was observed only at week 12 (mg/g creatinine, C12: 13.11±1.4 vs F12: 57.6±2.5#). Fructose overload leads to an increase in the urinary L-DOPA/DA ratio from 4th week, along with SBP elevation and natriuresis decrease, preceding microalbuminuria, which was detected at the 12th week. The urinary L-DOPA/DA ratio could be an even earlier predictor than microalbuminuria to detect renal dysfunction in fructose hypertension suggesting that an impaired renal DA metabolism could be involved in sodium retention and blood pressure elevation.