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Combined lack of estrogen receptors α and β affects vascular iNOS protein expression

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Abstract

Endothelial and vascular smooth muscle cells express both estrogen receptor (ER) α and β. Recent findings indicate that vascular ERβ and ERα may substitute for one another. Here, we investigate vascular morphology, contractility and protein expression in intact aorta from adult (4 months old) female mice lacking both ERα and ERβ (DERKO). The body weights were 17% higher (P<0.01) in DERKO than in wild-type mice. Vascular morphology, investigated in paraffin sections from aorta stained with hematoxylin-eosin or van Gieson, was identical in DERKO and wild-type mice. Endothelial cells were clearly visible in aorta of both DERKO and wild-type animals. Morphometric analysis of media thickness and wall to lumen ratio using a computerized image analyzing system demonstrated no differences between the two groups of mice. The vascular expression of endothelial nitric oxide synthase (eNOS, NOS III) and inducible nitric oxide synthase (iNOS, NOS II) was investigated using Western blotting. Aorta from both DERKO and wild-type mice expressed iNOS protein, but the iNOS expression was 3 times lower (P<0.05) in DERKO compared to wild-type mice. No difference in eNOS protein level between the two groups of animals was observed. Force responses to noradrenaline, determined either in the absence or in the presence of the nitric oxide synthase inhibitor l-NAME and the cyclo-oxygenase inhibitor indomethacin, were unaffected by the lack of functional ERα/ERβ. In summary, combined lack of functional ERα and ERβ lowers the vascular expression of iNOS but has no effects on morphology, eNOS expression, and noradrenaline sensitivity in the intact aorta.

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Acknowledgements

The authors gratefully thank Prof. Jan-Åke Gustafsson, Karolinska Institute, Huddinge University Hospital, Sweden, and Dr. Stefan Nilsson, KaroBio AB, Huddinge, Sweden, for kindly providing us with the DERKO and wild-type mice. We also gratefully thank Trine Fischer at Taconic M&B, Silkeborg, Denmark, for helping us with the genotyping of the mice.

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Authors and Affiliations

  1. Department of Physiological Sciences, Lund University, BMC F12, 221 84, Lund, Sweden

    M. Liang, E. Ekblad, M.-L. Lydrup & B.-O. Nilsson

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  1. M. Liang
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  2. E. Ekblad
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  3. M.-L. Lydrup
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  4. B.-O. Nilsson
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Correspondence to B.-O. Nilsson.

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This study was supported by the Swedish Medical Research Council (grant no. K99–0X-13017-01A), the Swedish Heart and Lung Foundation, KaroBio AB and the Åke Wiberg, Magnus Bergvall and Crafoord Foundations.

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Liang, M., Ekblad, E., Lydrup, ML. et al. Combined lack of estrogen receptors α and β affects vascular iNOS protein expression. Cell Tissue Res 313, 63–70 (2003). https://doi.org/10.1007/s00441-003-0731-3

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