Defective renal dopamine function and sodium-sensitive hypertension in adult ovariectomized Wistar rats: role of the cytochrome P-450 pathway.
We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of the total Na(+)-K(+)-ATPase (NKA) α1-subunit (Di Ciano LA, Azurmendi PJ, Toledo JE, Oddo EM, Zotta E, Ochoa F, Arrizurieta EE, Ibarra FR. Clin Exp Hypertens 35: 475-483, 2013). Upon high sodium (HS) intake, ovariectomized (oVx) rats developed 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 P-4504A (CYP4A) expression, and in 20-HETE production, while MBP kept normal. Blockade of the D1 receptor (D1R) with the D1-like receptor antagonist SCH 23390 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 < 0.05), NKA was more dephosphorylated than in IFHS, and CYP4A expression or 20-HETE production did not change. Blockade of D1R in oVxHS rats changed neither NKA phosphorylation state nor sodium excretion or MBP. D2R and PKCα expression did not vary among groups. The alteration of the renal DA system produced by ovariectomy could account for the defective NKA phosphorylation, the inefficient excretion of sodium load, and the development of salt-sensitive hypertension.
Instituto de Investigaciones Médicas A Lanari, Buenos Aires University, Buenos Aires, Argentina;
Luis A
LA
Di Ciano
Instituto de Investigaciones Médicas A Lanari, Buenos Aires University, Buenos Aires, Argentina;
Pablo J
PJ
Azurmendi
Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina;
Cecilia
C
Colombero
Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina;
Gloria
G
Levin
Instituto de Investigaciones Médicas A Lanari, Buenos Aires University, Buenos Aires, Argentina;
Elisabet M
EM
Oddo
Instituto de Investigaciones Médicas A Lanari, Buenos Aires University, Buenos Aires, Argentina; CONICET, Buenos Aires, Argentina.
Elvira E
EE
Arrizurieta
Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina;
Susana
S
Nowicki
Instituto de Investigaciones Médicas A Lanari, Buenos Aires University, Buenos Aires, Argentina; Departamento de Fisiología, Facultad de Medicina, Buenos Aires University, Buenos Aires, Argentina; and ilanari@pinos.com ibarraf@hotmail.com.
Fernando R
FR
Ibarra
D000375:Aging; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006973:Hypertension / Q000503:physiopathology; D010052:Ovariectomy / Q000379:methods; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D012982:Sodium, Dietary / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D017447:Receptors, Dopamine D1; D017673:Sodium Chloride, Dietary; D012982:Sodium, Dietary; D003577:Cytochrome P-450 Enzyme System; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine
CYP4A-20-HETE; Na+-K+-ATPase phosphorylation; dopamine D1 receptor; female hormones; ovariectomy; salt-sensitive hypertension