OBJECTIVE: 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.
OBJECTIVE: 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.
Authors: Wei Wang; Jinquan Cui; Xiaoxia Lu; Prashanth K Padakanti; Jinbin Xu; Stanley M Parsons; Robert R Luedtke; Nigam P Rath; Zhude Tu Journal: J Med Chem Date: 2011-07-20 Impact factor: 7.446
Authors: Richa Aishwarya; Chowdhury S Abdullah; Naznin S Remex; Shafiul Alam; Mahboob Morshed; Sadia Nitu; Brandon Hartman; Judy King; Mohammad Alfrad Nobel Bhuiyan; A Wayne Orr; Christopher G Kevil; Md Shenuarin Bhuiyan Journal: Am J Pathol Date: 2021-10-25 Impact factor: 4.307