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Journal of Endocrinology (2008) 197, 447-462    DOI: 10.1677/JOE-08-0070
© 2008 Society for Endocrinology

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REVIEW

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Inmaculada C Villar, Adrian J Hobbs and Amrita Ahluwalia1

Department of Pharmacology, University College London, Medical Sciences Building, Gower Street, London WC1E 6BT, UK1 Clinical Pharmacology, Barts and The London Medical School, William Harvey Research Institute, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK

(Correspondence should be addressed to A Ahluwalia; Email: a.ahluwalia{at}qmul.ac.uk)

The vascular endothelium plays a crucial role in the regulation of vascular homeostasis by controlling vascular tone, coagulation, and inflammatory responses. These actions are exerted by endothelial factors including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The greater incidence of cardiovascular disease (CVD) in men and postmenopausal women compared with premenopausal women implies a vasoprotective phenotype of females, which may be influenced by sex hormones. These hormones, particularly estrogen, have modulatory effects on the endothelium and circulating cells that have been implicated in vascular inflammation and in the development of CVD. EDHF seems to be the predominant endothelial factor in the resistance vasculature of females and this mediator could afford the beneficial cardiovascular risk profile observed in premenopausal woman. In this review, we discuss sex differences in EDHF biology and how sex hormones can modulate EDHF responses. We also review the implication of sex hormone-dependent regulation of EDHF in inflammatory processes, platelet function, and repair after vascular damage, each of which have a critical role in several aspects of the pathogenesis of CVD.







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