Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta.
The aim of the present study was to evaluate the effect of overstimulation of beta-adrenoceptors on vascular inflammatory mediators. Wistar rats were treated with the beta-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-1beta (124% and 125%) and IL-6 (231% and 40%) compared with controls but did not change TNF-alpha expression. The nuclear-to-cytoplasmatic protein expression ration of the NF-kappaB p65 subunit was increased by isoproterenol treatment (51%); in addition, it reduced the cytoplasmatic expression of IkappaB-alpha (52%) in aortas. An electrophoretic mobility shift assay was performed using the aorta, and increased NF-kappaB 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 beta-adrenoceptors increased proinflammatory cytokines and upregulated NF-kappaB 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 beta-adrenergic stimulation.
Davel
Ana Paula C
AP
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas I, Universidade de São Paulo, Sala 225, São Paulo 05508-900, Brazil.
Fukuda
Livia E
LE
De Sá
Larissa Lima
LL
Munhoz
Carolina D
CD
Scavone
Cristoforo
C
Sanz-Rosa
David
D
Cachofeiro
Victoria
V
Lahera
Vicente
V
Rossoni
Luciana V
LV
D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D006439:Hemodynamics / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007279:Injections, Subcutaneous; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012980:Sodium Salicylate / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000072000:NF-KappaB Inhibitor alpha; D010656:Phenylephrine; D013792:Thalidomide; D013482:Superoxide Dismutase; D007545:Isoproterenol; D000109:Acetylcholine; D012980:Sodium Salicylate