Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells.

Nevzati, Edin; Shafighi, Maziar; Bakhtian, Kamran D; Treiber, Hannes; Fandino, Javier; Fathi, Ali Reza (2015). Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells. In: Fandino, Javier; Marbacher, Serge; Fathi, Ali-Reza; Muroi, Carl; Keller, Emanuela (eds.) Neurovascular Events After Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement: Vol. 120 (pp. 141-145). Springer 10.1007/978-3-319-04981-6_24

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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.


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.


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 (eNOS(p)).


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.

Item Type:

Book Section (Book Chapter)


04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Plastic, Reconstructive and Aesthetic Surgery

UniBE Contributor:

Shafighi, Maziar


600 Technology > 610 Medicine & health






Acta Neurochirurgica Supplement






Jörg Arnoldi

Date Deposited:

26 Jan 2015 12:24

Last Modified:

05 Dec 2022 14:39

Publisher DOI:


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