**Part 9**

**Estrogens and Endothelium** 

320 Basic and Clinical Endocrinology Up-to-Date

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**14** 

 *Spain* 

**Estradiol Regulation of Prostanoids** 

*Research Foundation- INCLIVA, Hospital Clínico UniversitarioValencia* 

The endothelium is a continuous cellular monolayer lining the interior of the blood vessels and heart. Classically considered to exert its actions only as a mechanical barrier, also plays important roles in vascular physiology. Endothelium participates in numerous metabolic and regulatory functions such as the control of primary hemostasis, blood coagulation and fibrinolysis, interaction with lipoprotein metabolism, platelet and leukocyte interactions with the vessel wall, presentation of histocompatibility antigens, regulation of vascular tone and growth, and of blood pressure. The endothelium exerts these actions through the release of such vasoactive compounds as prostacyclin, thromboxane A2, nitric oxide (NO), bradykinin, endothelin, angiotensin, and free radicals that control the functions of vascular smooth muscle cells and of circulating blood cells

The integrity and functionality of the arterial endothelium play a crucial role in the physiology of circulation (Filipe *et al.*, 2008) and, as a consequence, in preventing the development of cardiovascular diseases, whose genesis is currently considered a consequence of the anatomical and functional disruption of the endothelium (Spyridopoulos *et al.*, 1997). When the ability of the endothelial cells to release relaxing is reduced, and in particular if the propensity to produce contractile factors is enhanced, endothelial dysfunction appears as a first step in the sequence of events that leads to atherosclerosis and coronary disease. Thus, no single mechanism is responsible for all endothelium dependent responses and their modulation by pathophysiological states leads to endothelial dysfunction characterized by an imbalance in endothelial regulators

Clinical and experimental data support the consideration of endothelium as a target for estradiol and other sexual hormones. A number of studies have demonstrated a favourable profile for estrogens in both experimental animal, as well as in *in vitro* models (Turgeon *et al.*, 2006). However, the protective effect detected in a considerable number of observational clinical studies (Barrett-Connor & Grady, 1998) has not been confirmed by randomized placebo-controlled trials (Hulley *et al.*, 1998; Grady *et al.*, 2002), which described clinical complications, such as thrombosis in veins and coronary arteries, developed in postmenopausal women during the administration of exogenous hormones

**1. Introduction** 

(Ross, 1999; Vapaatalo & Mervaala, 2001).

(Vanhoutte *et al.*, 2009).

(Cano *et al.*, 2007).

**Production in Endothelium** 

Susana Novella and Carlos Hermenegildo *Department of Physiology, University of Valencia* 
