JACC
HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
 QUICK SEARCH:   [advanced]


     


J Am Coll Cardiol, 2002; 40:991-997
© 2002 by the American College of Cardiology Foundation
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sanada, S.
Right arrow Articles by Kitakaze, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sanada, S.
Right arrow Articles by Kitakaze, M.

EXPERIMENTAL STUDY

Opening of the adenosine triphosphate-sensitive potassium channel attenuates cardiac remodeling induced by long-term inhibition of nitric oxide synthesis

Role of 70-kDa S6 kinase and extracellular signal-regulated kinase

Shoji Sanada, MD*, Koichi Node, MD*, Hiroshi Asanuma, MD*, Hisakazu Ogita, MD*, Seiji Takashima, MD*, Tetsuo Minamino, MD*, Masanori Asakura, MD*, Yulin Liao, MD*, Akiko Ogai, BS{dagger}, Jiyoong Kim, MD{dagger}, Masatsugu Hori, MD, FACC* and Masafumi Kitakaze, MD, FACC{dagger},*

* Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
{dagger} Cardiology Division of Medicine, National Cardiovascular Center, Suita, Japan

Manuscript received April 4, 2001; revised manuscript received April 26, 2002, accepted May 24, 2002.

* Reprint requests and correspondence: Dr. Masafumi Kitakaze, Cardiovascular Division of Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita Osaka 565-8565, Japan.
kitakaze{at}hsp.ncvc.go.jp

OBJECTIVES: We examined whether the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel openers (KCOs) block myocardial hypertrophy and whether the 70-kDa S6 kinase (p70S6K) or extracellular signal-regulated kinase (ERK)-dependent pathway is involved.

BACKGROUND: Long-term inhibition of nitric oxide (NO) synthesis induces cardiac hypertrophy independent of blood pressure, by increasing protein synthesis in vivo. The KCOs attenuate calcium overload and confer cardioprotection against ischemic stress, thereby preventing myocardial remodeling.

METHODS: Twelve Wistar-Kyoto rat groups underwent eight weeks of the drug treatment in combination with the NO synthase inhibitor N{omega}-nitro-L-arginine methyl ester (L-NAME), the inactive isomer D{omega}-nitro-L-arginine methyl ester, KCOs (nicorandil, 3 and 10 mg/kg per day, or JTV-506, 0.3 mg/kg per day), or the KATP channel blocker glibenclamide. The L-NAME was also used with hydralazine, the p70S6K inhibitor rapamycin, or the mitogen-activated protein kinase inhibitor PD98059. Finally, the left ventricular weight (LVW) to body weight (BW) ratio was quantified, followed by histologic examination and kinase assay.

RESULTS: The L-NAME increased blood pressure and LVW/BW, as compared with the control agent. The KCOs and hydralazine equally cancelled the increase in blood pressure, whereas only KCOs blocked the increase in LVW/BW and myocardial hypertrophy induced by L-NAME. The L-NAME group showed both p70S6K and ERK activation in the myocardium (2.3-fold and 2.0-fold increases, respectively), as compared with the control group, which was not reversed by hydralazine. Selective inhibition of either p70S6K or ERK blocked myocardial hypertrophy. The KCOs prevented the increase in activity only of p70S6K. Glibenclamide reversed the effect of nicorandil in the presence of L-NAME.

CONCLUSIONS: The KCOs modulate p70S6K, not ERK, to attenuate myocardial hypertrophy induced by long-term inhibition of NO synthesis in vivo.

Abbreviations and Acronyms
  ANOVA
  analysis of variance
  ATP
  adenosine triphosphate
  BW
  body weight
  D-NAME
  D{omega}-nitro-L-arginine methyl ester
  ERK
  extracellular signal-regulated kinase
  KATP
  adenosine triphosphate-sensitive potassium
  KCO
  adenosine triphosphate-sensitive potassium channel opener
  L-NAME
  N{omega}-nitro-L-arginine methyl ester
  LVW
  left ventricular weight
  NO
  nitric oxide
  p70S6K
  70-kDa S6 kinase
  PKC
  protein kinase C




This article has been cited by other articles:


Home page
J Am Coll CardiolHome page
T.-M. Lee, M.-S. Lin, and N.-C. Chang
Effect of ATP-Sensitive Potassium Channel Agonists on Ventricular Remodeling in Healed Rat Infarcts
J. Am. Coll. Cardiol., April 1, 2008; 51(13): 1309 - 1318.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
T. Minamino and M. Hori
Protecting endothelial function: A novel therapeutic target of ATP-sensitive potassium channel openers
Cardiovasc Res, February 1, 2007; 73(3): 448 - 449.
[Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
Y. Xia, S. Javadov, T. X. Gan, T. Pang, M. A. Cook, and M. Karmazyn
Distinct KATP Channels Mediate the Antihypertrophic Effects of Adenosine Receptor Activation in Neonatal Rat Ventricular Myocytes
J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 14 - 21.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
T.-M. Lee, M.-S. Lin, C.-H. Tsai, and N.-C. Chang
Effect of pravastatin on left ventricular mass in the two-kidney, one-clip hypertensive rats
Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2705 - H2713.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
D. Bell, Y.-Y. Zhao, E. J. Kelso, E. M. McHenry, L. M. Rush, V. M. Lamont, D. P. Nicholls, and B. J. McDermott
Upregulation of adrenomedullin and its receptor components during cardiomyocyte hypertrophy induced by chronic inhibition of nitric oxide synthesis in rats
Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H904 - H914.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
S. Sanada, K. Node, T. Minamino, S. Takashima, A. Ogai, H. Asanuma, H. Ogita, Y. Liao, M. Asakura, J. Kim, et al.
Long-Acting Ca2+ Blockers Prevent Myocardial Remodeling Induced by Chronic NO Inhibition in Rats
Hypertension, April 1, 2003; 41(4): 963 - 967.
[Abstract] [Full Text] [PDF]




HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
Copyright © 2002 by the American College of Cardiology Foundation.