Dehydroepiandrosterone-mediated stimulation of sigma-1 receptor activates Akt-eNOS signaling in the thoracic aorta of ovariectomized rats with abdominal aortic banding

Md Shenuarin Bhuiyan, Hideaki Tagashira, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Objective: Decreased dehydroepiandrosterone (DHEA) levels are associated with endothelial dysfunction and increased cardiovascular mortality in postmenopausal women. Using ovariectomized rats, we first defined whether expression of sigma-1 receptor (Sig-1R) in the aorta is regulated following pressure overload (PO) and also after DHEA treatment. We also investigated effects of DHEA known as Sig-1R agonist on impaired Akt/endothelial nitric oxide synthase (eNOS) signaling in the thoracic aorta under PO. Research design/methods: Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis 2 weeks later. DHEA (15 and 30 mg/kg) was administered orally once a day for 14 days starting from 2 weeks after the aortic banding. Results: Time course study indicated that expression of Sig-1R expression and eNOS decreased time dependently in the thoracic aorta from 1 to 4 weeks after PO. DHEA treatment significantly inhibited the decreased Sig-1R expression in the thoracic aorta. The DHEA treatment also significantly restored PO-induced impaired Akt phosphorylation and stimulated eNOS protein expression with concomitant increased Akt-mediated eNOS phosphorylation (Ser1177). We did not find any changes in the phosphorylation of ERK1/2 and PKCα in the aorta following PO and after treatment with DHEA. Conclusion: We here reported, for the first time, that DHEA treatment induces the upregulation and stimulation of Sig-1R in the thoracic aorta that stimulate Sig-1R-mediated Akt-eNOS signaling pathways in ovariectomized rats under PO.

Original languageEnglish
Pages (from-to)219-230
Number of pages12
JournalCardiovascular Therapeutics
Volume29
Issue number4
DOIs
Publication statusPublished - 2011 Aug

Keywords

  • Dehydroepiandrosterone (DHEA)
  • Endothelial nitric oxide synthase (eNOS)
  • Myocardial hypertrophy
  • Protein kinase B (Akt)
  • Sigma-1 receptor (Sig-1R)

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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