Effects of dexamethasone short-time treatment: role of renin-angiotensin-system and autonomic nervous system

Abstract

Dexamethasone (Dex) is a synthetic glucocorticoid widely used because of its potent anti-inflammatory and antiallergic effects. However when chronically administered, several side effects such as body weight loss, muscle atrophy, hyperglycemia and hyperinsulinemia, blood pressure (BP) increase, among others are present. Among the mechanism responsible for BP increase there are reduced nitric oxide expression and bioavailability, increases in renin angiotensin system (RAS) activity, increases in sympathetic activity and oxidative stress. Considering that many clinical treatments with DEX are shorter it is important to investigate the possible mechanisms involved in the BP control after DEX treatment. Therefore, the aim of this study is to analyze the effects of a short time DEX treatment on the renin angiotensin system and the autonomic balance to the heart. Eighty rats will be divided into four groups: 1/ control group, treated with saline for one day (C1, n = 20); 2/ DEX group, treated with dexamethasone for one day (D1, 1 mg / kg, i.p., n=20); 3/ control group, treated by five days with saline (C5, n = 20) and 4/ DEX group treated with dexamethasone for five days (D5, 1 mg / kg, i.p., n=20) for . All animals will be weighed during treatment and at the last day they will underwent a carotid artery catheterization surgery for blood pressure (BP) and heart rate (HR) measurements. After 24 h, resting BP and HR will be registered and the BP signals will be used for sympathetic, parasympathetic and autonomic balance to the heart evaluations through spectral analysis technique. Left ventricle (LV) and tibialis anterior (TA) muscle will be removed for quantification of gene expression (RT-PCR real time) and protein level (Western Blotting) of RAS components. Data will be presented as mean ± standard error of the means. Two way analysis of variance (ANOVA) will be used, with Tukey post-hoc when necessary (±<0.05). (AU)