Involvement of endogenous ouabain-like compound in the cardiac hypertrophic process in vivo.
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 microg/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 microg/kg/h). Administration of exogenous ouabain (1 nM to 100 microM) 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 alpha-adrenergic agonist phenylephrine (1 microM) was markedly enhanced by ouabain (100 microM) (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.
Skoumal
Réka
R
1st Department of Medicine, Semmelweis University, Budapest H-1083, Hungary; Szentágothai János Knowledge Center, Semmelweis University, Budapest H-1085, Hungary.
Szokodi
István
I
Aro
Jani
J
Földes
Gábor
G
Göoz
Mónika
M
Seres
Leila
L
Sármán
Balázs
B
Lakó-Futó
Zoltán
Z
Papp
Lajos
L
Vuolteenaho
Olli
O
Leppäluoto
Juhani
J
DeChâtel
Rudolf
R
Ruskoaho
Heikki
H
Tóth
Miklós
M
D000315:Adrenalectomy; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D015152:Blotting, Northern; D002298:Cardenolides / Q000097:blood*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000097:blood* / Q000139:chemically induced / Q000235:genetics; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000097:blood*; D015854:Up-Regulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002298:Cardenolides; D012333:RNA, Messenger; D012503:Saponins; D014662:Vasoconstrictor Agents; C034504:digoxin-like factors; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D009638:Norepinephrine