Renal dopamine alteration increases Na+, K+-ATPase expression and activity and correlates with hypertension in fructose overloaded rats

PUYÓ AM; RUKAVINA MIKUSIC NL; KOUYOUMDZIAN NM; KRAVETZ MC; DEL MAURO J; PANDOLFO M; LEE HJ; PEREDO H; CAO G; GIRONACCI MM; TOBLLI JE; FERNÁNDEZ BE; CHOI MR

Milan

Encuentro; 25th European Meeting on Hypertension and Cardiovascular Protection; 2015

European Society of Hypertension

Objective: Metabolic and hemodynamic changes induced by fructoseoverload could be associated with a renal dopaminergic system impairment which mayaffect activity and expression of renal Na+, K+-ATPasecontributing to sodium retention and hypertension. The objective of our studywas to determine changes in renal dopamine (DA) production through themeasurement of urinary L-dopa/DA index and its relationship with natriuresis, renalexpression and activity of Na+, K+-ATPase and systolicblood pressure (SBP).Designand method: MaleSprague Dawley rats were studied: a) Controls(C4, C8, C12:  tapwater to drink) and b) Fructose overloaded: (F4, F8, F12: 10%w/v of fructose solution to drink), treatedduring 4, 8 and 12 weeks (n=8rats/group/period). Urinary L-dopa and DA were determined by HPLC; diuresis and sodium were measured in 24 hour urine samples. SBP was determined by tail-cuff method. Thespecific activity of Na+, K+-ATPase and its proteinexpression weredetermined by enzymatic and immunofluorescence/western blot techniques, respectively. Results: Fructoseoverload increased SBP (mmHg, C4: 121±8 vs F4: 145±1*; C8: 130±4 vs F8: 161±10#;C12: 133±5 vs F12: 163±4#), urinary L-dopa/DA index (C4: 0.49±0.05vs 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#) and decreased urinary sodium excretion.A positive correlation was observed throughout all thetreatment period between SBP  and urinaryL-dopa/DA index (R2=0.7816, p=0.002). These changeswere accompanied by an increase in renalNa+, K+-ATPase activity(nmol/mg/min, C4: 120±12 vs F4: 172±16*; C8: 124±16 vs F8: 186±17*; C12: 140±18vs F12: 223±21#) and its protein expression (arbitraryunits, renal cortex: C8: 1.00±0.03 vs F8: 1.94±0.34*; medulla: C4: 1.00±0.03 vsF4: 1.54±0.02#; C8: 1.00±0.02 vs F8: 1.39±0.07#; C12:1.00±0.02 vs F12: 1.24±0.10*). *p<0.05, #p<0.01. Conclusions: Fructoseoverload leads to an increase in the urinary L-dopa/DA index from 4thweek of treatment that correlates positively with SBP, along with an elevationin both, renal Na+,K+-ATPase activity and expression. These findings are in accordance with adecrease in natriuresis, postulating the L-dopa/DA ratio as a good index toevaluate an early renal dysfunction.