Endothelial function, vascular reactivity and gender differences in the cardiovascular system.

Time for primary review 40 days. A marked gender difference exists in the prevalence and severity of cardiovascular disease, even after adjustment for traditional vascular risk factors, which are more prevalent in males [1]. This has led to an interest in the role of sex steroids themselves in the promotion or inhibition of atherogenic events. As endothelial dysfunction is an early and important event in atherogenesis [2] and appears to predict adverse coronary outcomes [3], gender differences in endothelial function and the effects of hormonal therapy on vascular function have been the focus of considerable research interest. The normal vascular endothelium regulates arterial tone, platelet and leukocyte interactions, coagulation, fibrinolysis and vascular growth [4]. Measurement of endothelial function in the systemic arteries has become established as an important method for the detection of early (pre-symptomatic) arterial abnormalities in humans [5]. Ultrasound-detected endothelial dysfunction in peripheral arteries correlates significantly with coronary endothelial dysfunction [6], as well as with the extent and severity of coronary atherosclerosis [7]. The availability of a non-invasive method for the reproducible measurement of endothelium-dependent dilatation has facilitated the study of the interactions between sex hormones and arterial function, in both males and females. The normal vascular endothelium is only one cell layer thick, separating the blood and vascular smooth muscle. The endothelium responds to physical and chemical stimuli via the synthesis and/or release of regulatory substances affecting vascular tone and growth, thrombosis and thrombolysis and platelet and leukocyte interactions with the endothelium. Substances released by the endothelium include nitric oxide (NO), prostacyclin, endothelins, interleukins, endothelial growth factors, adhesion molecules, plasminogen inhibitors and von Willebrand factor [4,8–10]. The pivotal role of the endothelium in regulating vascular smooth muscle tone has only recently been appreciated [11]. The existence of an endothelium-derived … * Corresponding author. Tel.: +61-2-9515-6519; fax: +61-2-9550-6262 davidc{at}card.rpa.cs.nsw.gov.au