RENAL NATRIURETIC SYSTEMS ALTERATION IN FRUCTOSE OVERLOADED RATS

PUYÓ AM; KOUYOUMDZIAN NM; RUKAVINA MIKUSIC NL; ROUVIER E; CANTÚ SM; LEE HJ; TOBLLI JE; FERNÁNDEZ BE; CHOI MR

París

Congreso; 26th European Meeting on Hypertension and Cardiovascular Protection; 2016

European Society of Hypertension

Objective:Metabolic and hemodynamic changes induced by a high fructose diet could beassociated with an impairment of renal natriuretic systems, which contributesto sodium retention and hypertension. There is little evidence about renal dopamine (DA) andtype-A natriuretic peptide (ANP) interaction on blood pressure elevation inthis model. The aim of this study was to evaluate both natriuretic systems in fructose-overloadedrats. Design and method: MaleSprague Dawley rats were randomly assigned: a) Controls (C, tap water to drink) and b)Fructose overloaded: (F, 10% w/v offructose to drink), treated during 4, 8 and 12 weeks (n=8 rats/group/period). Urinary L-dopa and DA (HPLC); diuresis,creatinine and sodium were measured in 24 hour urine samples; and ANP (ELISA), triglycerides,glycemia, cholesterol, insulinemia, creatinine and sodium in plasma. Systolicblood pressure (SBP) was determined bytail-cuff method and renal tissue protein expression of L-dopatransporter (LAT-2), D1R and NPR-A receptors by Westernblot. Results: Fructose overloadincreased 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#).An elevation in cortex LAT-2 expression (arbitrary units) (C4: 1.00±0.02 vs. F4:1.30±0.04*; C8: 1.00±0.5 vs. F8: 1.23±0.09*; C12: 1.00±0.02 vs. F12:1.40±0.01*) and medulla (C8: 1.00±0.01 vs. F8: 1.42±0.02*; C12: 1.00±0.01 vs.F12: 1.42±0.04*); and a decrease D1R in cortex (C4:1.00±0.05 vs. F4: 0.72±0.08*; C8: 1.00±0.5 vs. F8: 0.75±0.07*) were found. PlasmaANP decrease (C8: 1.61±0.10 vs. F8: 1.30±0.08*; C12: 1.65±0.32 vs. F12:1.04±0.16*) along with a lower NPR-A expression in medulla (C4:1.00±0.05 vs. F4: 0.81±0.02*; C8: 1.00±0.04 vs. F8: 0.80±0.03*;C12: 1.00±0.03 vs. F12: 0.81±0.01#) were also observed (*p<0.05, #p<0.01vs. C). Conclusions: Fructose overloadleads to an increase in the urinary L-dopa/DA index from 4th week oftreatment that correlates positively with blood pressure elevation. Furthermorethe decrease in the natriuretic systems DA and ANP seems to be related to thephysiopathology of hypertension in this model.