Defective Renal Dopamine Function and Sodium Sensitive Hypertension in Adult Ovariectomized Wistar Rats: Role of the Cytochrome P450 Pathway

DI CIANO L; AZURMENDI P; COLOMBERO C; LEVIN, G; ODDO E; ARRIZURIETA, E; NOWICKI S; IBARRA, F

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2015 vol. 308 p. 1358 - 1368

1931-857X

We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of total Na+, K+-ATPase α 1subunit (NKA). Upon high sodium (HS) intake ovariectomized (oVx) rats developed a defective NKA phosphorylation, a decrease in sodium excretion, and an increment in mean blood pressure (MBP). Since NKA phosphorylation is modulated by dopamine (DA), the aim of this study was to compare the intracellular response of the renal DA system leading to NKA phosphorylation upon sodium challenge in intact female (IF) and oVx rats. In IF rats HS caused an increase in urinary DA and sodium, in NKA phosphorylation state, in Cytochrome P4504A (CYP4A) expression and in 20-HETE production, while MBP kept normal. Blockade of D1R with the D1-like receptor antagonist SCH23390 in IFHS rats shifted NKA into a more dephosphorylated state, decreased sodium excretion by 50 % and increased MBP. In oVxNS rats, D1R expression was reduced and D3R expression was increased, and under HS intake sodium excretion was lower and MBP higher than in IFHS rats (both p