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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/H211    most recent 00581.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Davel, A. P. C. Articles by Rossoni, L. V. PubMed PubMed Citation Articles by Davel, A. P. C. Articles by Rossoni, L. V.

Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta

¹Department of Physiology and Biophysics and ²Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil; and ³Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain

Submitted 17 May 2007 ; accepted in final form 14 May 2008

The aim of the present study was to evaluate the effect of overstimulation of β-adrenoceptors on vascular inflammatory mediators. Wistar rats were treated with the β-adrenoceptor agonist isoproterenol (0.3 mg·kg^–1·day^–1 sc) or vehicle (control) for 7 days. At the end of treatment, the right carotid artery was catheterized for arterial and left ventricular (LV) hemodynamic evaluation. Isoproterenol treatment increased LV weight but did not change hemodynamic parameters. Aortic mRNA and protein expression were quantified by real-time RT-PCR and Western blot analysis, respectively. Isoproterenol enhanced aortic mRNA and protein expression of IL-1β (124% and 125%) and IL-6 (231% and 40%) compared with controls but did not change TNF- expression. The nuclear-to-cytoplasmatic protein expression ration of the NF-B p65 subunit was increased by isoproterenol treatment (51%); in addition, it reduced the cytoplasmatic expression of IB- (52%) in aortas. An electrophoretic mobility shift assay was performed using the aorta, and increased NF-B DNA binding (31%) was observed in isoproterenol-treated rats compared with controls (P < 0.05). Isoproterenol treatment increased phenylephrine-induced contraction in aortic rigs (P < 0.05), which was significantly reduced by superoxide dismutase (150 U/ml) and sodium salicylate (5 mM). Cotreatment with thalidomide (150 mg·kg^–1·day^–1 for 7 days) also reduced hyperreactivity to phenylephrine induced by isoproterenol. In conclusion, overstimulation of β-adrenoceptors increased proinflammatory cytokines and upregulated NF-B in the rat aorta. Moreover, local oxidative stress and the proinflammatory state seem to play key roles in the altered vascular reactivity of the rat aorta induced by chronic β-adrenergic stimulation.

β-adrenoceptor; blood vessels; cytokines; nuclear factor-B