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

Abstract

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.

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

“…This is a plausible association that plays a crucial role in vascular homeostasis, which may be regulated by sex hormones, especially estrogen 26. Estrogen contributes to regulation of vascular tone, modulates recruitment of circulating cells, effects platelet function, and plays a role in processes responsible for vascular repair 26. Gene variants in women modulate the function of estrogen, its receptors, and are implicated in aspects of cardiovascular inflammation, platelet function, and vascular repair 26, 27…”

Effect of age and gender on the progression of adult vascular dysfunction in a mouse model of fetal programming lacking endothelial nitric oxide synthase

“…This is, however, speculative and requires further investigation. Estrogen improves vascular tone by decreasing myointimal smooth muscle cell proliferation (40), inhibiting tumor necrosis factor-␣-induced apoptosis in endothelial cells, (32), and inducing NOS3 in different tissues (45,50).…”

The effect ofHypericum perforatumon isolated rat aorta

“…Previous researchers have described the inhibition of iNOS by HP (Tedeschi et al, 2003;Saad et al, 2008;Kraus et al, 2010). Endothelial cell xantine oxidase forms ROS (Villar et al, 2008). A set of experiments has been done on xantine oxidase system of vascular tissue by using commercially available form of HP and this study has shown a dose-dependant ROS suppression (Hunt et al, 2001).…”

“…The vascular endothelium has a crucial role in the modulation of the vascular functions such as contraction and relaxation of the vascular smooth muscle (Demirci et al, 2005;Moncada and Higgs, 2006;Demirci et al, 2008;Villar et al, 2008). This delicate balance is achieved by synthesizing and secreting vasoactive agents, mainly nitric oxide (NO), prostaglandins, endothelium-derived hyperpolarizing factor (EDHF) (Moncada & Higgs, 2006;Villar et al, 2008) and endothelins (Whittle & Moncada, 1990).…”

“…This delicate balance is achieved by synthesizing and secreting vasoactive agents, mainly nitric oxide (NO), prostaglandins, endothelium-derived hyperpolarizing factor (EDHF) (Moncada & Higgs, 2006;Villar et al, 2008) and endothelins (Whittle & Moncada, 1990). Endothelial dysfunction contributes some pathologic conditions, including vasoconstriction, hypertension, atherosclerosis, platelet aggregation and inflammation in association with impaired production or activity of NO, reactive oxygen species (ROS) and cytokines (Herman & Moncada, 2005).…”