Corticosteroids and Endothelial Dysfunction

Corticosteroids and endothelial dysfunction Assessment of endothelial-mediated relaxation in situ is rapidly becoming the standard gauge of individual susceptibility to future cardiovascular dysfunction (Hadi et al 2005). In this issue of Vascular Health and Risk Management, Turner and colleagues (2005), in a pilot investigation, have proposed the concept that endothelial dysfunction in patients with systemic lupus erythematosus, but with no known cardiovascular disease, is the result of exposure to corticosteroids. Even though the study by Turner and colleagues (2005) has a small sample size and may not have the desired power to conclusively indicate the relationship between endothelial dysfunction and corticosteroids use, it is worth considering the possible basis for such an association. An interesting angle of this hypothesis is the impact of corticosteroids on the plasma glucose levels and insulin. The metabolic actions of corticoid steroid, namely cortisol, are well recognized, and it is counted among the counter-regulatory stress hormones. Infusion of hydrocortisone is believed to increase plasma glucose, free fatty acid, and insulin concentrations, and is thus believed to increase metabolic rate in healthy individuals (Brillon et al 1995). Moreover, despite an elevated insulin concentration, hypercortisolemia results in a significantly higher plasma glucose concentration (Nielsen et al 2003). In addition, during the infusion of glucose in healthy subjects, the integrated glycemic response above baseline is higher in the presence of hydrocortisone than saline infusion, which suggests that plasma glucose level is less rigorously controlled and seems to remain elevated for a longer duration in presence of the glucocorticoid (Nielsen et al 2003). Of interest, is that treatment with prednisolone, which reportedly causes insulin resistance, hyperinsulinemia, and hyperglucagonemia (Gravholt et al 2002), as well as infusion of hydrocortisone, also seems to result in insulin resistance (Nielsen et al 2003). There is now ample evidence in the literature that provides both an acute and a chronic link between glucose and endothelial dysfunction in animals and humans (Ceriello 2004; Triggle et al 2005). Some compelling early evidence was presented by Kawano and colleagues (1999), which indicated that flow-mediated vasodilation is decreased after glucose loading in normal subjects and patients with type 2 diabetes mellitus, and it was suggested that suppression of endothelium-dependent vasodilation was probably due to the production of oxygen-derived free radicals. Moreover, Title et al (2000) reported that the acute transient decrease in flow-mediated dilation in healthy subjects by oral glucose could be prevented by vitamins C and E. …