Dexamethasone- (Dex-) induced hypertension is associated with enhanced oxidative stress. Lactoferrin (LF) is an iron-binding glycoprotein with antihypertensive properties. In this study, we investigated the effect of chronic administration of LF on oxidative stress and hypertension upon Dex administration. Male Wistar rats were treated by Dex (30？μg/kg/day subcutaneously) or saline for 14 days. Oral bovine LF (30, 100, 300？mg/kg) was given from day 8 to 14 in a reversal study. In a prevention study, rats received 4 days of LF treatment followed by Dex and continued during the test period. Systolic blood pressure (SBP) was measured using tail-cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) value were determined. Dexamethasone significantly increased SBP and plasma H2O2 level and decreased thymus and body weights. LF lowered and dose dependently prevented Dex-induced hypertension. LF prevented body weight loss and significantly reduced the elevated plasma H2O2 and increased FRAP values. Chronic administration of LF strongly reduced the blood pressure and production of ROS and improved antioxidant capacity in Dex-induced hypertension, suggesting the role of inhibition of oxidative stress as another mechanism of antihypertensive action of LF. 1. Introduction Chronic administration of glucocorticoid, especially at supraphysiological doses, leads to elevated systolic blood pressure, in man and animals [1]. Increased vascular sensitivity to glucocorticoids has been also demonstrated in patients with essential hypertension [2]. Dexamethasone- (Dex-) induced hypertension is associated with decreased antioxidant levels, enhanced oxidative stress and reduced nitric oxide (NO) level [3, 4]. Overproduction of reactive oxygen species (ROS) occurs in this model of hypertension like many other forms of hypertension. Interaction between ROS and NO leads to reduced NO availability and vasoconstriction [5]. An increasing body of evidence has shown the role of antioxidants in preventing increased oxidative stress and blood pressure in Dex-induced hypertension [6–8]. Lactoferrin (LF) is a multifunctional iron-binding glycoprotein. Different biological fluids especially milk and also neutrophilic granules contain LF [9]. LF receptors are found in various cell types such as lymphocytes, platelets, macrophages, dopaminergic neurons, megacaryocytes, and endothelial cells. Some of these receptors are involved in LF uptake. In the cerebral endothelial cells, LF
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