J Physiol Volume 577, Number 3, 945-955, December 15, 2006 DOI: 10.1113/jphysiol.2006.121939
The oestrogen receptor ß contributes to sex related differences in endothelial function of murine small arteries via EDHF
Leonid Luksha1,
Lucilla Poston2,
Jan-Åke Gustafsson3,
Kjell Hultenby4 and
Karolina Kublickiene1
1 Institution for Clinical Science, Intervention and Technology, Department of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital, Huddinge Campus, Stockholm, Sweden
2 Division of Reproduction and Endocrinology, Kings College London, London, UK
3 Department of Biosciences and Nutrition
4 Clinical Research Centre, Department of Laboratory Medicine, Karolinska, Institutet, Novum, Stockholm, Sweden
Sex related differences in cardiovascular function have been reported in oestrogen receptor ß knockout (ERßKO) mice. In this study we examined the role of endothelium-derived hyperpolarizing factor (EDHF) in differences in small artery endothelial function between ERßKO and wild-type (WT) mice. Small femoral arteries were isolated from ERßKO and WT mice and mounted on a wire myograph. Concentration–response curves to ACh were compared before and after incubation with inhibitors of nitric oxide (NO) and prostacyclin (PGI2) synthesis. Comparison of the expression of the principal vascular connexins (Cx37, 40 and 43), implicated in EDHF-mediated dilatation were undertaken by immunohistochemistry. Vascular ultrastructure was studied by transmission and scanning electron microscopy. ACh-induced relaxation of arteries (< 200 µm internal diameter) was greater in WT females versus males and was attributable to a greater EDHF component of relaxation. This sex difference was absent in ERßKO mice. Arteries from ERßKO males (but not females) were more sensitive to ACh compared to WT. The pharmacological evidence and morphological prerequisite for involvement of gap junctions in EDHF-mediated responses was confirmed in male arteries. The absence of ERß had no influence on expression of main Cx subtypes within vascular wall or on ultrastructure and morphology of the endothelium. The data suggest that in WT male mice, ERß reduces EDHF-mediated relaxation through gap junction communication.
(Received 28 September 2006;
accepted after revision 9 October 2006;
first published online 12 October 2006)
Corresponding author K. Kublickiene: Institution for Clinical Science, Intervention and Technology (CLINTEC), Department of Obstetrics and Gynecology, Karolinska Institute, Karolinska University Hospital–Huddinge campus, 14186 Stockholm, Sweden. Email: karolina.kublickiene{at}ki.se
Copyright © 2006 The Physiological Society.
