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Targeting sigma-1 receptor with fluvoxamine ameliorates pressure-overload-induced hypertrophy and dysfunctions.

AbstractOBJECTIVE:
We here investigated the effect of sigma-1 receptor (Sig-1R) stimulation with fluvoxamine on myocardial hypertrophy, cardiac functional recovery and defined mechanisms underlying its cardioprotective action.
METHODS:
Wistar rats subjected to bilateral ovariectomy (OVX) were treated with abdominal aortic banding between the right and left renal arteries. To confirm the cardioprotective role of Sig-1R stimulation, we treated the rats with Sig-1R agonist (fluvoxamine, 0.5 and 1 mg/kg) orally once a day for 4 weeks after the onset of aortic banding.
RESULTS:
Interestingly, the expression of Sig-1R in the left ventricle (LV) decreased significantly 4 weeks after pressure overload (PO)-induced hypertrophy in OVX rats. The fluvoxamine administration significantly attenuated PO-induced myocardial hypertrophy with concomitant increase in the expression of Sig-1R in LV. Fluvoxamine also attenuated hypertrophy-induced impaired LV functions. The cardioprotective effect of fluvoxamine was nullified by treatment with Sig-1R antagonist (NE-100; 1 mg/kg). Fluvoxamine treatment significantly restored PO-induced impaired eNOS and Akt activity in the LV.
CONCLUSION:
We here found, for the first time, the potential role of Sig-1R expression in the heart in attenuating PO-induced hypertrophy in OVX rats. Fluvoxamine treatment protects PO-induced cardiac injury via upregulation of Sig-1R and stimulation of Sig-1R-mediated Akt-eNOS signaling in ovariectomized rats.
AuthorsMd Shenuarin Bhuiyan, Hideaki Tagashira, Norifumi Shioda, Kohji Fukunaga
JournalExpert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 14 Issue 10 Pg. 1009-22 (Oct 2010) ISSN: 1744-7631 [Electronic] England
PMID20722474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anisoles
  • Cardiotonic Agents
  • Propylamines
  • Receptors, Glycine
  • Receptors, sigma
  • Serotonin Uptake Inhibitors
  • sigma-1 receptor
  • strychnine-insensitive glycine receptor
  • N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
  • Fluvoxamine
Topics
  • Animals
  • Anisoles (administration & dosage, pharmacology)
  • Blood Pressure (drug effects)
  • Cardiotonic Agents (administration & dosage, pharmacology)
  • Female
  • Fluvoxamine (administration & dosage, pharmacology)
  • Heart (physiopathology)
  • Humans
  • Hypertrophy, Left Ventricular (drug therapy, physiopathology, prevention & control)
  • Myocardium (metabolism)
  • Ovariectomy
  • Propylamines (administration & dosage, pharmacology)
  • Rats
  • Rats, Wistar
  • Receptors, Glycine (antagonists & inhibitors)
  • Receptors, sigma (agonists, antagonists & inhibitors, metabolism)
  • Serotonin Uptake Inhibitors (administration & dosage, pharmacology)
  • Signal Transduction
  • Up-Regulation

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