Alteración del sistema dopaminérgico renal en un modelo de hipertensión arterial por sobrecarga de fructosa: utilidad del índice L-dopa/dopamina urinario como predictor de daño renal

RUKAVINA MIKUSIC NL; KOUYOUMDZIAN NM; DEL MAURO J; CAO G; TRIDA VA; GIRONACCI MM; PUYÓ AM; TOBLLI JE; FERNÁNDEZ BE; CHOI MR

Mendoza

Congreso; XXIV Congreso Argentino de Hipertensión Arterial (SAHA); 2017

Sociedad Argentina de Hipertensión Arterial (SAHA)

Introduction: Renal dopaminergicsystem (RDS) promotes sodium excretion and anti-inflammatory actions. A high fructose dietinduces metabolic and hemodynamic changes that could be associated with animpairment of the RDS, leading to renal inflammation, sodium retention andarterial hypertension. Aim: to evaluate RDS state and its associationwith the development of hypertension and overexpression of renal inflammatorymarkers in fructose overloaded (FO) rats. Methods: MaleSprague Dawley rats were assigned to Control (C, tap water) or FO (10% w/v offructose solution) groups, during 4, 8 and 12 weeks (n=8/group/period). Urinary L-dopa anddopamine (DA), diuresis and albuminuria were determined.Systolic blood pressure (SBP) and metabolic parameters weremeasured. Western blot analysis of renal expression of D1R, NFκβ, IL-6,TNF-α, TGF-β1 and nephrin were performed.  Results: FO increased SBP (mmHg, C4:121±8 vs. F4: 145±1*; C8: 130±4 vs. F8: 161±10#; C12: 133±5 vs. F12: 163±4#),which positively correlated (R2=0.78; p<0.002) to urinary L-dopa/DA index(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#). A significant decrease of D1R expression wasaccompanied by a significant increase in nFκβ, IL-6, TNF-α, TGF-β1 expressionsince week 4. Microalbuminuria (C12:13.11±1.4 vs F12:57.6±2.5#) and asignificant decrease in nephrin expression (C12: 1.00±0.10 vs. F12: 0.73±0.05#)were only observed at week 12. (*p<0.05, #p<0.01 vs. C). Conclusion:FO was associated with an increased L-dopa/DA index and decreased D1R expressionsince week 4 of treatment. The RDS dysfunction was accompanied by an increase inblood pressure levels and renal expression of inflammatory markers in allexperimental periods. Alteration of L-dopa/DA index could be postulated as an earliermarker of renal dysfunction than structural damage evidenced by microalbuminuriaand decreased nephrin expression in week 12 of FO.