Defective renal dopamine D1 receptor function and Na+, K+-ATPase phosphorylation in ovariectomized adult Wistar rats

LUIS DI CIANO; PABLO J AZURMENDI; ELISABET M ODDO; GLORIA LEVIN; BELEN BORSINI; JORGE TOLEDO; VERONICA DE LUCA SAROBE; ELVIRA ARRIZURIETA; FERNANDO IBARRA

Buenos Aires, Argentina

Simposio; RENAL REGULATION OF BLOOD PRESSURE. ROLE OF ANGIOTENSIN AND DOPAMIN; 2012

AMERICAN PHYSIOLOGICAL SOCIETY?S LATIN AMERICAN INITIATIVE.

  We showed that ovariectomized (oVx) Wistar rats consuming high sodiun (HS) had both a less phosphorylated Na+, K+-ATPase (NKA) and a reduced natriuresis resulting in Na+ sensitive hypertension. Being NKA phospho-state regulated by dopamine (DA) via D1 receptor mediated mechanism, we tested whether NKA and renal DA might be involves in the hypertensive response to salt load. Rats oVx at 60 days old and intact female (IF) were studied at 150days of life. The last 5 days they had been feed with normal (NS) or HS diet (1% NaCl in drinking water). Afterwards, rats received D1R antagonist (SCH 23390,1mg/kg bwt/d sc)DA infusion (1ug/kg bwt/min) or vehicle. Mean blood pressure (MBP), Na+ excretion (UNa+*V) and DA (uDA) were measured. Expression of D1R and its phosphi-state of NKA at Ser23 (p-NKA) were determined in renal homogenates. uDA increased from NS to HS in all groups (p<0.05). After D1R antagonist tratment in IF HS, UNa+*V diminished by 50% and MBP increased to 140±2mmHg (p<0.05), while its effect was negligible in oVx-HS group. D1R blockade blunted the increase in p-NKA induces by HS in IF (p<0.01). Instead, D1R antagonist had no effect in oVx. DA infusion enhanced UNa+*V in IF and HS (p<0.05, both). This response was absent in oVx. D1R expression showed a band at 55kD and 75 kD. The 55 kD diminished in