title: Fenofibrate and pioglitazone do not ameliorate the altered vascular reactivity in aorta of isoproterenol-treated rats.
abstract: Chronic stimulation of beta-adrenoceptors with isoproterenol induces alteration of vascular reactivity and increases local pro-inflammatory cytokines. We investigated whether fenofibrate and pioglitazone, PPAR-alpha and -gamma agonists, respectively, improve the changes in vascular reactivity induced by isoproterenol. Wistar rats received isoproterenol (0.3 mg x kg x day, SC) or vehicle (CT) plus fenofibrate (alpha, 100 mg x kg x day, PO), pioglitazone (gamma, 2.5 mg.kg.day, PO), or water for 7 days. In aortas, isoproterenol treatment enhanced the maximal response (Rmax) to phenylephrine (10 to 10 M) compared to CT as previously demonstrated. The effects of endothelium removal (E-) or L-NAME incubation (100 microM) on the phenylephrine response were smaller in isoproterenol-treated animals compared to CT while superoxide dismutase (SOD, 150 U/mL) significantly reduced the Rmax to phenylephrine to CT levels. Neither fenofibrate nor pioglitazone changed the effects induced by isoproterenol in aorta. E-, L-NAME, or SOD effects were similar between CTalpha and CT. However, pioglitazone per se increased Rmax to phenylephrine (CT: 59 +/- 4 versus CTgamma: 72 +/- 5 % of contraction to KCl). E- or L-NAME effects were reduced in CTgamma compared to CT, and SOD normalized the altered reactivity to phenylephrine in the CTgamma group. In conclusion, neither fenofibrate nor pioglitazone ameliorates the altered vascular reactivity present in aorta from isoproterenol-treated rats. Moreover, pioglitazone per se induced endothelial dysfunction and increased phenylephrine-induced contraction in aorta.
authors.affiliation: Department of Physiological and Biophysical Sciences, Institute of Biomedical Science, University of Sao Paulo, São Paulo, Brazil.
authors.forename: Lívia Emy
authors.initials: LE
authors.lastname: Fukuda
authors.forename: Ana Paula Couto
authors.initials: AP
authors.lastname: Davel
authors.forename: Sidney
authors.initials: S
authors.lastname: Verissimo-Filho
authors.forename: Lucia Rossetti
authors.initials: LR
authors.lastname: Lopes
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
authors.forename: Luciana Venturini
authors.initials: LV
authors.lastname: Rossoni
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D011345:Fenofibrate / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D000077205:Pioglitazone; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000318:Adrenergic beta-Agonists; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D011189:Potassium Chloride; D013482:Superoxide Dismutase; D007545:Isoproterenol; D011345:Fenofibrate; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone