Skip to main content

Advertisement

SpringerLink
Log in

Effects of long-term ouabain treatment on blood pressure, sodium excretion, and renal dopamine D1 receptor levels in rats

  • Original Paper
  • Published:
Journal of Comparative Physiology B Aims and scope Submit manuscript

Abstract

To examine the effects of chronic ouabain treatment on blood pressure (BP), sodium excretion, and renal dopamine D1 receptor level, male Sprague-Dawley (SD) rats were treated with ouabain (27.8 μg kg−1 d−1) intraperitoneally for 5 weeks, and systolic blood pressure (SBP) were recorded weekly. After 5 weeks, sodium excretion and dopamine D1 receptor agonist fenoldopam-mediated natriuresis were measured, and the expression and phosphorylation levels of the renal cortical dopamine D1 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 D1 receptor expression levels were reduced, and D1 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 D1 receptor function serves as a mechanism responsible for sodium retention, and this contributes to the hypertension induced by chronic ouabain treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aperia A (2001) Regulation of sodium/potassium ATPase activity: impact on salt balance and vascular contractility. Curr Hypertens Rep 3:165–171

    Article  CAS  PubMed  Google Scholar 

  • Barnard ML, Olivera WG, Rutschman DM, Bertorello AM, Katz AI, Sznajder JI (1997) Dopamine stimulates sodium transport and liquid clearance in rat lung epithelium. Am J Respir Crit Care Med 156:709–714

    CAS  PubMed  Google Scholar 

  • Boireau A, Meunier M, Imperato A (1998) Ouabain-induced increase in dopamine release from mouse striatal slices is antagonized by riluzole. J Pharm Pharmacol 50:1293–1297

    CAS  PubMed  Google Scholar 

  • Cargnelli G, Trevisi L, Debetto P, Luciani S, Bova S (2000) Effect of long-term ouabain treatment on contractile responses of rat aortae. J Cardiovasc Pharmacol 35:538–542

    Article  CAS  PubMed  Google Scholar 

  • Diniz PH, Silva JH, Gomez MV, Guatimosim C, Gomez RS (2007) Halothane increases non-vesicular [(3)H]dopamine release from brain cortical slices. Cell Mol Neurobiol 27:757–770

    Article  CAS  PubMed  Google Scholar 

  • Doris PA (2000) Renal proximal tubule sodium transport and genetic mechanisms of essential hypertension. J Hypertens 18:509–519

    Article  CAS  PubMed  Google Scholar 

  • Eklof AC, Holtback U, Sundelof M, Chen S, Aperia A (1997) Inhibition of COMT induces dopamine-dependent natriuresis and inhibition of proximal tubular Na+, K+-ATPase. Kidney Int 52:742–747

    Article  CAS  PubMed  Google Scholar 

  • Felder RA, Eisner GM, Jose PA (2000) D1 dopamine receptor signaling defect in spontaneous hypertension. Acta Physiol Scand 168:245–250

    Article  CAS  PubMed  Google Scholar 

  • Ferrandi M, Manunta P (2000) Ouabain-like factor: is this the natriuretic hormone. Curr Opin Nephrol Hypertens 9:165–171

    Article  CAS  PubMed  Google Scholar 

  • Ferrandi M, Barassi P, Molinari I, Torielli L, Tripodi G, Minotti E, Bianchi G, Ferrari P (2005) Ouabain antagonists as antihypertensive agents. Curr Pharm Des 11:3301–3305

    Article  CAS  PubMed  Google Scholar 

  • Ferrari P, Torielli L, Ferrandi M, Padoani G, Duzzi L, Florio M, Conti F, Melloni P, Vesci L, Corsico N, Bianchi G (1998) PST 2238: a new antihypertensive compound that antagonizes the long-term pressor effect of ouabain. J Pharmacol Exp Ther 285:83–94

    CAS  PubMed  Google Scholar 

  • Ge H, Lü ZR (2006) Changes in renal sodium transport during hypertension development in ouabain-hypertensive rats. Nan Fang Yi Ke Da Xue Xue Bao 26:1404–1407

    CAS  PubMed  Google Scholar 

  • Hamlyn JM, Hamilton BP, Manunta P (1996) Endogenous ouabain, sodium balance and blood pressure: a review and a hypothesis. J Hypertens 14:151–167

    Article  CAS  PubMed  Google Scholar 

  • Huang BS, Leenen FH (1999) Brain renin-angiotensin system and ouabain-induced sympathetic hyperactivity and hypertension in Wistar rats. Hypertension 34:107–112

    CAS  PubMed  Google Scholar 

  • Jose PA, Eisner GM, Felder RA (2000) Renal dopamine and sodium homeostasis. Curr Hypertens Rep 2:174–183

    Article  CAS  PubMed  Google Scholar 

  • Jose PA, Eisner GM, Felder RA (2002) Role of dopamine receptors in the kidney in the regulation of blood pressure. Curr Opin Nephrol Hypertens 11:87–92

    Article  PubMed  Google Scholar 

  • Ladines CA, Zeng C, Asico LD, Sun X, Pocchiari F, Semeraro C, Pisegna J, Wank S, Yamaguchi I, Eisner GM, Jose PA (2001) Impaired renal D(1)-like and D(2)-like dopamine receptor interaction in the spontaneously hypertensive rat. Am J Physiol Regul Integr Comp Physiol 281:R1071–R1078

    CAS  PubMed  Google Scholar 

  • Li M, Martin A, Wen C, Turner SW, Lewis LK, Whitworth JA (1995) Long-term ouabain administration does not alter blood pressure in conscious Sprague-Dawley rats. Clin Exp Pharmacol Physiol 22:919–923

    Article  CAS  PubMed  Google Scholar 

  • Manunta P, Rogowski AC, Hamilton BP, Hamlyn JM (1994) Ouabain induced hypertension in the rat: relationship among plasma and tissue ouabain and blood pressure. J Hypertens 12:549–560

    Article  CAS  PubMed  Google Scholar 

  • Manunta P, Messaggio E, Ballabeni C, Sciarrone MT, Lanzanic C, Ferrandi M, Hamlyn JM, Cusi D, Galletti G, Salt Sensitivity Study Group of the Italian Society of Hypertension (2001) Plasma ouabain-like factor during acute and chronic changes in sodium balance in essential hypertension. Hypertension 38:198–203

    CAS  PubMed  Google Scholar 

  • Manunta P, Ferrandi M, Messaggio E, Ferrari P (2006) A new antihypertensive agent that antagonizes the prohypertensive effect of endogenous ouabain and adducin. Cardiovasc Hematol Agents Med Chem 4:61–66

    Article  CAS  PubMed  Google Scholar 

  • Manunta P, Maillard M, Tantardini C, Simonini M, Lanzani C, Citterio L, Stella P, Casamassima N, Burnier M, Hamlyn JM, Bianchi G (2008) Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension. J Hypertens 26:914–920

    Article  CAS  PubMed  Google Scholar 

  • Marwaha A, Banday AA, Lokhandwala MF (2004) Reduced renal dopamine D1 receptor function in streptozotocin-induced diabetic rats. Am J Physiol Renal Physiol 286:F451–F457

    Article  CAS  PubMed  Google Scholar 

  • Rossoni LV, Cunha V, Franca A, Vassallo DV (1999) The influence of nanomolar ouabain on vascular pressor responses is modulated by the endothelium. J Cardiovasc Pharmacol 34:887–892

    Article  CAS  PubMed  Google Scholar 

  • Rossoni LV, Salaices M, Marín J, Vassallo DV, Alonso MJ (2002a) Alterations in phenylephrine-induced contractions and the vascular expression of Na+, K+- ATPase in ouabain-induced hypertension. Br J Pharmacol 135:771–781

    Article  CAS  PubMed  Google Scholar 

  • Rossoni LV, Salaices M, Miguel M, Briones AM, Barker LA, Vassallo DV, Alonso MJ (2002b) Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors. Am J Physiol Heart Circ Physiol 283:H2110–H2118

    CAS  PubMed  Google Scholar 

  • Rossoni LV, Xavier FE, Moreira CM, Falcochio D, Amanso AM, Tanoue CU, Carvalho CR, Vassallo DV (2006) Ouabain-induced hypertension enhances left ventricular contractility in rats. Life Sci 79:1537–1545

    Article  CAS  PubMed  Google Scholar 

  • Sanada H, Jose PA, Harzen-Martin D, Yu PY, Xu J, Bruns DE, Phipps J, Carey RM, Felder RA (1999) Dopamine-1 receptor coupling defect in renal proximal tubule cells in hypertension. Hypertension 33:1036–1042

    CAS  PubMed  Google Scholar 

  • Schoner W (2002) Endogenous cardiac glycosides, a new class of steroid hormones. Eur J Biochem 269:2440–2448

    Article  CAS  PubMed  Google Scholar 

  • Schoner W, Scheiner-Bobis G (2007) Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth. Am J Physiol Cell Physiol 293:C509–C536

    Article  CAS  PubMed  Google Scholar 

  • Tian G, Dang C, Lu Z (2001) The change and significance of the Na+-K+-ATPase alpha-subunit in ouabain-hypertensive rats. Hypertens Res 24:729–734

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by Natural Science Foundation of China (30570732, 30871043 to Yuan ZY, 30700320 to Liu Y); “985 Project” by Ministry of Education of China (to Yuan ZY); grant for New Century Outstanding Investigator by Ministry of Education of China (NCET-04-0942 to Yuan ZY). The experiments performed comply with current Chinese laws.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi’an Jiaotong University, 277 West Yanta Road, 710061, Xi’an, Shaanxi, China

    Yurong Zhang, Zuyi Yuan & Yanping Ren

  2. Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, 710061, Xi’an, Shaanxi, China

    Zuyi Yuan

  3. Department of Nephrology, Second Affiliated Hospital of Medical School, Xi’an Jiaotong University, 710004, Xi’an, Shaanxi, China

    Heng Ge

Authors
  1. Yurong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zuyi Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heng Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanping Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zuyi Yuan.

Additional information

Communicated by G. Heldmaier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, Y., Yuan, Z., Ge, H. et al. Effects of long-term ouabain treatment on blood pressure, sodium excretion, and renal dopamine D1 receptor levels in rats. J Comp Physiol B 180, 117–124 (2010). https://doi.org/10.1007/s00360-009-0391-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00360-009-0391-z

Keywords

Search

Navigation