Renal dopaminergic system dysfunction is associated to high blood pressure and inflammation in fructose overload induced metabolic syndrome

PUYÓ AM; RUKAVINA MIKUSIC NL; KOUYOUMDZIAN NM; ROBBESAUL GD; ALVAREZ PRIMO M; LEE HJ; TOBLLI JE; FERNÁNDEZ BE; CHOI MR

Milán

Congreso; 27th European Meeting on Hypertension and Cardiovascular Protection; 2017

European Society of Hypertension

Objective: The renal dopaminergic system (RDS) promotes sodium excretion and anti-infl ammatory actions. Fructose overload (FO) produces in the rat hemodynamic and metabolic changes similar to the human metabolic syndrome. These changes are associated to an impairment of the RDS, leading to renal infl ammation, sodium retention and blood pressure elevation. The aim of this study was to evaluate RDS state and its relation to hypertension and overexpression of renal infl ammatory markers in the FO experimental model. Design and method: Six groups of male Sprague Dawley rats (six weeks at the beginning of the treatment) were studied: Control (C4, C8 and C12, tap water to drink) or FO (F4, F8 and F12, 10% w/v of fructose solution to drink), during 4, 8 and 12 weeks (n  =  8/group/period). Urinary L-dopa and dopamine (DA) (HPLC), diuresis and albuminuria were determined. Systolic blood pressure (SBP) (tail cuff) and metabolic parameters were measured. Western blot analysis of renal expression of dopamine 1 receptor (D1R), NFkappa-beta, IL-6, TNF-alpha, TGFbeta1 and nephrin were performed.Results: 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#), 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 signifi cant decrease in the D1R expression was related to a signifi cant increase in nFkappa-beta, IL-6, TNF-alpha, TGF-beta1 expression since week 4. Microalbuminuria (C12:13.11  ±  1.4 vs F12:57.6  ±  2.5#) and a decrease in nephrin expression (C12: 1.00  ±  0.10 vs. F12: 0.73  ±  0.05#) were observed only at week 12. (*p  <  0.05, #p  <  0.01 vs. C). Conclusions: Fructose overload was associated to an L-dopa/DA index increase and D1R expression decrease since week 4 of treatment. The renal dopaminergic system dysfunction was accompanied by an increase in blood pressure levels and renal expression of infl ammatory markers in all experimental periods studied. Alteration of L-dopa/DA index could be an earlier marker of renal dysfunction than the structural damage evidenced by microalbuminuria and decreased nephrin expression in week 12 of fructose treatment.