Involvement of endogenous ouabain-like compound in the cardiac hypertrophic process in vivo

R. Skoumal, I. Szokodi, Jani Aro, Gábor Földes, Mónika Göoz, Leila Seres, Balázs Sármán, Zoltán Lakó-Futó, L. Papp, Olli Vuolteenaho, Juhani Leppäluoto, Rudolf deChâtel, Heikki Ruskoaho, Miklós Tóth

Research output: Article

10 Citations (Scopus)

Abstract

The Na+/K+-ATPase inhibitor ouabain has been shown to trigger hypertrophic growth of cultured cardiomyocytes; however, the significance of endogenous ouabain-like compound (OLC) in the hypertrophic process in vivo is unknown. Here we characterized the involvement of OLC in left ventricular (LV) hypertrophy induced by norepinephrine (NE) and angiotensin II (Ang II) infusions in rats. Administration of NE (300 μg/kg/h) via subcutanously implanted osmotic minipumps for 72 h resulted in a significant increase in left ventricular weight to body weight (LVW/BW) ratio (P <0.001) and a substantial up-regulation of atrial natriuretic peptide (ANP) gene expression (13.2-fold, P <0.001). NE infusion induced a transient increase in plasma OLC levels at 12 h (P <0.05), which returned to control levels by 72 h. Adrenalectomy markedly reduced both basal and NE-induced increase in plasma OLC levels. LVW/BW ratio was not modulated by adrenalectomy; however, ANP gene expression was blunted by 44% (P <0.01) and 47% (P <0.05) at 12 and 72 h, respectively. In agreement, adrenalectomy reduced up-regulation of ANP without affecting LV mass in rats infused with Ang II (33 μg/kg/h). Administration of exogenous ouabain (1 nM to 100 μM) for 24 h had no effect on ANP gene expression in cultured neonatal rat ventricular myocytes. However, the up-regulation of ANP mRNA levels induced by the α-adrenergic agonist phenylephrine (1 μM) was markedly enhanced by ouabain (100 μM) (5.6-fold vs. 9.6-fold, P <0.01). These data show that OLC as an adrenal-derived factor may be required for the induction LV ANP gene expression during the hypertrophic process.

Original languageEnglish
Pages (from-to)1303-1310
Number of pages8
JournalLife Sciences
Volume80
Issue number14
DOIs
Publication statusPublished - márc. 13 2007

Fingerprint

Ouabain
Atrial Natriuretic Factor
Gene expression
Adrenalectomy
Norepinephrine
Gene Expression
Rats
Up-Regulation
Angiotensin II
Body Weight
Plasmas
Weights and Measures
Adrenergic Agonists
Level control
Left Ventricular Hypertrophy
Phenylephrine
Cardiac Myocytes
Muscle Cells
Messenger RNA
Growth

ASJC Scopus subject areas

  • Pharmacology

Cite this

Involvement of endogenous ouabain-like compound in the cardiac hypertrophic process in vivo. / Skoumal, R.; Szokodi, I.; Aro, Jani; Földes, Gábor; Göoz, Mónika; Seres, Leila; Sármán, Balázs; Lakó-Futó, Zoltán; Papp, L.; Vuolteenaho, Olli; Leppäluoto, Juhani; deChâtel, Rudolf; Ruskoaho, Heikki; Tóth, Miklós.

In: Life Sciences, Vol. 80, No. 14, 13.03.2007, p. 1303-1310.

Research output: Article

Skoumal, R, Szokodi, I, Aro, J, Földes, G, Göoz, M, Seres, L, Sármán, B, Lakó-Futó, Z, Papp, L, Vuolteenaho, O, Leppäluoto, J, deChâtel, R, Ruskoaho, H & Tóth, M 2007, 'Involvement of endogenous ouabain-like compound in the cardiac hypertrophic process in vivo', Life Sciences, vol. 80, no. 14, pp. 1303-1310. https://doi.org/10.1016/j.lfs.2006.12.026
Skoumal, R. ; Szokodi, I. ; Aro, Jani ; Földes, Gábor ; Göoz, Mónika ; Seres, Leila ; Sármán, Balázs ; Lakó-Futó, Zoltán ; Papp, L. ; Vuolteenaho, Olli ; Leppäluoto, Juhani ; deChâtel, Rudolf ; Ruskoaho, Heikki ; Tóth, Miklós. / Involvement of endogenous ouabain-like compound in the cardiac hypertrophic process in vivo. In: Life Sciences. 2007 ; Vol. 80, No. 14. pp. 1303-1310.
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AU - Aro, Jani

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AU - Göoz, Mónika

AU - Seres, Leila

AU - Sármán, Balázs

AU - Lakó-Futó, Zoltán

AU - Papp, L.

AU - Vuolteenaho, Olli

AU - Leppäluoto, Juhani

AU - deChâtel, Rudolf

AU - Ruskoaho, Heikki

AU - Tóth, Miklós

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N2 - The Na+/K+-ATPase inhibitor ouabain has been shown to trigger hypertrophic growth of cultured cardiomyocytes; however, the significance of endogenous ouabain-like compound (OLC) in the hypertrophic process in vivo is unknown. Here we characterized the involvement of OLC in left ventricular (LV) hypertrophy induced by norepinephrine (NE) and angiotensin II (Ang II) infusions in rats. Administration of NE (300 μg/kg/h) via subcutanously implanted osmotic minipumps for 72 h resulted in a significant increase in left ventricular weight to body weight (LVW/BW) ratio (P <0.001) and a substantial up-regulation of atrial natriuretic peptide (ANP) gene expression (13.2-fold, P <0.001). NE infusion induced a transient increase in plasma OLC levels at 12 h (P <0.05), which returned to control levels by 72 h. Adrenalectomy markedly reduced both basal and NE-induced increase in plasma OLC levels. LVW/BW ratio was not modulated by adrenalectomy; however, ANP gene expression was blunted by 44% (P <0.01) and 47% (P <0.05) at 12 and 72 h, respectively. In agreement, adrenalectomy reduced up-regulation of ANP without affecting LV mass in rats infused with Ang II (33 μg/kg/h). Administration of exogenous ouabain (1 nM to 100 μM) for 24 h had no effect on ANP gene expression in cultured neonatal rat ventricular myocytes. However, the up-regulation of ANP mRNA levels induced by the α-adrenergic agonist phenylephrine (1 μM) was markedly enhanced by ouabain (100 μM) (5.6-fold vs. 9.6-fold, P <0.01). These data show that OLC as an adrenal-derived factor may be required for the induction LV ANP gene expression during the hypertrophic process.

AB - The Na+/K+-ATPase inhibitor ouabain has been shown to trigger hypertrophic growth of cultured cardiomyocytes; however, the significance of endogenous ouabain-like compound (OLC) in the hypertrophic process in vivo is unknown. Here we characterized the involvement of OLC in left ventricular (LV) hypertrophy induced by norepinephrine (NE) and angiotensin II (Ang II) infusions in rats. Administration of NE (300 μg/kg/h) via subcutanously implanted osmotic minipumps for 72 h resulted in a significant increase in left ventricular weight to body weight (LVW/BW) ratio (P <0.001) and a substantial up-regulation of atrial natriuretic peptide (ANP) gene expression (13.2-fold, P <0.001). NE infusion induced a transient increase in plasma OLC levels at 12 h (P <0.05), which returned to control levels by 72 h. Adrenalectomy markedly reduced both basal and NE-induced increase in plasma OLC levels. LVW/BW ratio was not modulated by adrenalectomy; however, ANP gene expression was blunted by 44% (P <0.01) and 47% (P <0.05) at 12 and 72 h, respectively. In agreement, adrenalectomy reduced up-regulation of ANP without affecting LV mass in rats infused with Ang II (33 μg/kg/h). Administration of exogenous ouabain (1 nM to 100 μM) for 24 h had no effect on ANP gene expression in cultured neonatal rat ventricular myocytes. However, the up-regulation of ANP mRNA levels induced by the α-adrenergic agonist phenylephrine (1 μM) was markedly enhanced by ouabain (100 μM) (5.6-fold vs. 9.6-fold, P <0.01). These data show that OLC as an adrenal-derived factor may be required for the induction LV ANP gene expression during the hypertrophic process.

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KW - Atrial natriuretic peptide

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KW - Norepinephrine

KW - Ouabain

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