Increase in sympathetic nervous system is associated with beta-adrenoceptor (beta-AR) hyperactivation. This hyperactivation can be performed using chronic treatment with a non-selective beta-AR agonist, isoproterenol (ISO). We have previously demonstrated that ISO-treated rats show enhanced vasoconstrictor response induced by phenylephrine, impairment of nitric oxide (NO) bioavailability, as well as an increase in local synthesis of pro-inflammatory factors. In addition, stimulation of beta-AR could promote endocrine and local synthesis and release of angiotensin II and aldosterone. It is known that angiotensin II via AT1 receptors, and aldosterone via mineralocorticoid receptors (MR) cause endothelial dysfunction, oxidative stress and inflammation, by signaling cascade including the activation of MAP kinases and NF-kappaB nuclear factor. It has been shown that the antagonism of AT1 or MR improve the structural and functional cardiac alterations induced by ISO treatment. However, it is not clear whether a cross-talk involving beta-AR activation and rennin-angiotensin-aldoterone signaling could be involved in the vascular effects induced by ISO treatment. Therefore, the aim of this research is to investigate the possible effects of AT1 or MR antagonists in the vascular alteration induced by beta-adrenergic hyperactivation. For this, Wistar rats will be treated with ISO or vehicle and co-treated with AT1 or MR antagonists. The aorta and pulmonary artery will be isolated from these animals to perform vascular reactivity experiments, fluorescence measurements to infer the oxidative stress and NO in situ production and real time RT-PCR and Western blot for analysis of gene and protein expression of anti- and pro-oxidants enzymes, pro-inflammatory factors and MAP kinases.
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