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Estrogen Induces Nitric Oxide Production Via Nitric Oxide Synthase Activation in Endothelial Cells

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Neurovascular Events After Subarachnoid Hemorrhage

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 120))

Abstract

Introduction: 17β-estradiol (E2) has been found to induce vasodilation in the cardiovascular system and at physiological levels, resulting in prevention of cerebral vasospasm following subarachnoid hemorrhage (SAH) in animal models. The goal of this study was to analyze the cellular mechanism of nitric oxide (NO) production and its relation to E2, in vitro in brain and peripheral endothelial cells.

Methods: Human umbilical endothelial cells (HUVEC) and brain endothelial cells (bEnd.3) were treated with estradiol (E2, 0.1, 10, 100, and 1,000 nM), and supernatant was collected at 0, 5, 15, 30, 60, and 120 min for nitric oxide metabolome (nitrite, NO2) measurements. Cells were also treated with E2 in the presence of 1400W, a potent eNOS inhibitor, and ICI, an antagonist of estradiol receptors (ERs). Effects of E2 on eNOS protein expression were assessed with Western blot analysis.

Results: E2 significantly increased NO2 levels irrespective of its concentration in both cell lines by 35 % and 42 % (p < 0.05). The addition of an E2 antagonist, ICI (10 μM), prevented the E2-induced increases in NO2 levels (11 % p > 0.05). The combination of E2 (10 nM) and a NOS inhibitor (1400W, 5 μM) inhibited NO2 increases in addition (4 %, p > 0.05). E2 induced increases in eNOS protein levels and phosphorylated eNOS (eNOSp).

Conclusions: This study indicates that E2 induces NO level increases in cerebral and peripheral endothelial cells in vitro via eNOS activation and through E2 receptor-mediated mechanisms. Further in vivo studies are warranted to evaluate the therapeutic value of estrogen for the treatment of SAH-induced vasospasm.

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Conflict of Interest Statement

 None of the authors has any conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland

    Edin Nevzati MD, Javier Fandino MD & Ali Reza Fathi MD

  2. Department of Plastic, Reconstructive and Hand Surgery, University Hospital, Inselspital, University of Bern, Bern, Switzerland

    Maziar Shafighi MD

  3. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    Kamran D. Bakhtian MS & Hannes Treiber MD

Authors
  1. Edin Nevzati MD
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  2. Maziar Shafighi MD
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  3. Kamran D. Bakhtian MS
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  4. Hannes Treiber MD
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  5. Javier Fandino MD
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  6. Ali Reza Fathi MD
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Correspondence to Ali Reza Fathi MD .

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Editors and Affiliations

  1. Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland

    Javier Fandino

  2. Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland

    Serge Marbacher

  3. Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland

    Ali-Reza Fathi

  4. Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland

    Carl Muroi

  5. Department of Neurosurgery Neurointensive Care Unit, University Hospital Zurich, Zurich, Switzerland

    Emanuela Keller

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Nevzati, E., Shafighi, M., Bakhtian, K.D., Treiber, H., Fandino, J., Fathi, A.R. (2015). Estrogen Induces Nitric Oxide Production Via Nitric Oxide Synthase Activation in Endothelial Cells. In: Fandino, J., Marbacher, S., Fathi, AR., Muroi, C., Keller, E. (eds) Neurovascular Events After Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 120. Springer, Cham. https://doi.org/10.1007/978-3-319-04981-6_24

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  • DOI: https://doi.org/10.1007/978-3-319-04981-6_24

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  • Online ISBN: 978-3-319-04981-6

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