Effects of long-term ouabain treatment on blood pressure, sodium excretion, and renal dopamine D(1) receptor levels in rats.
To examine the effects of chronic ouabain treatment on blood pressure (BP), sodium excretion, and renal dopamine D(1) receptor level, male Sprague-Dawley (SD) rats were treated with ouabain (27.8 microg kg(-1) d(-1)) intraperitoneally for 5 weeks, and systolic blood pressure (SBP) were recorded weekly. After 5 weeks, sodium excretion and dopamine D(1) receptor agonist fenoldopam-mediated natriuresis were measured, and the expression and phosphorylation levels of the renal cortical dopamine D(1) receptor were confirmed by Western blot analysis. The effects of ouabain on fenoldopam-mediated inhibition of Na(+)-K(+)-ATPase activity were determined by colorimetric assays in human proximal tubular epithelial cells (HK-2 cells). After 5 weeks, the SBP in ouabain group was significantly higher than that in the control group (P < 0.01), but the sodium excretion and renal cortical D(1) receptor expression levels were reduced, and D(1) receptor phosphorylation levels were increased after ouabain treatment. Intravenous administration of fenoldopam caused an increased sodium excretion in control rats, but failed to induce natriuresis in ouabain-treated rats. In addition, fenoldopam induced a dose-respone (10(-9) to 10(-6) M) inhibition of Na(+)-K(+)-ATPase activity in HK-2 cells,but these effects were significantly diminished in HK-2 cells pretreated with nanomolar concentration of ouabain for 5 days (P < 0.01). We propose that the ouabain-induced reduction of the renal dopamine D(1) receptor function serves as a mechanism responsible for sodium retention, and this contributes to the hypertension induced by chronic ouabain treatment.
Zhang
Yurong
Y
Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, 277 West Yanta Road, 710061, Xi'an, Shaanxi, China.
Yuan
Zuyi
Z
Ge
Heng
H
Ren
Yanping
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000008:administration & dosage / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012964:Sodium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase