Peroxynitrite decomposition catalysts prevent myocardial dysfunction and inflammation in endotoxemic rats
Steve Lancel, PhD* ,
Stéphanie Tissier, MD*,
Serge Mordon, PhD*,
Xavier Marechal, PhD*,
Florence Depontieu, PhD ,
Arnaud Scherpereel, MD, PhD,
Claude Chopin, MD* and
Remi Neviere, MD, PhD*,*
* EA 2689, Université de Lille 2, Faculté de Médecine, Lille, France
Département de Physiologie, Faculté de Médecine, Lille, France
INSERM U416, Institut Pasteur de Lille, Lille, France
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Figure 1 Left ventricular developed pressure (LVDP), maximum rate of left ventricular pressure rise (dP/dtmax), and coronary perfusion pressure (CPP) of isolated and perfused heart from rats treated with saline (control), endotoxin (10 mg/kg), endotoxin and N-nitro-L-arginine methyl ester (LNAME) (50 mg/kg), endotoxin and mercaptoethylguanidine (MEG) sodium succinate (10 mg/kg), and endotoxin and 5,10,15,20-tetrakis(4-sulfonatophenyl)-porphyrinato iron (III) (FeTPPS) (30 mg/kg). See Methods section for treatment group design. Results are expressed as mean ± SEM (n = 8 in each group). *p < 0.01 compared with control; #p < 0.01 compared with endotoxin-treated rats.
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Figure 2 (A) Plasma rhodamine fluorescence intensity (n = 8 in each group) and (B) representative heart section (n = 3 in each group) stained for nitrotyrosine by immunohistochemistry of rats treated with saline, endotoxin (10 mg/kg), endotoxin and L-NAME (50 mg/kg), endotoxin and MEG sodium succinate (10 mg/kg), and endotoxin and FeTPPS (30 mg/kg). See Methods section for treatment group design. Results are expressed as mean ± SEM. *p < 0.01 compared with control; #p < 0.01 compared with endotoxin-treated rats. Abbreviations as in Figure 1.
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Figure 3 Effects of L-NAME (50 mg/kg), MEG sodium succinate (10 mg/kg), and FeTPPS (30 mg/kg) on endotoxin-induced heart I-kappa-B degradation and plasma tumor necrosis factor (TNF)-alpha levels. See Methods section for treatment group design. (A) Degradation of I-kappa-B (n = 5 in each group). Semiquantitative analysis was performed on the basis of relative I-kappa-B/G3PDH density. (B) Plasma TNF-alpha levels (n = 6 in each group). Results are expressed as mean ± SEM. *p < 0.01 compared with control; #p < 0.01 compared with endotoxin-treated rats. Abbreviations as in Figure 1.
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Figure 4 (A) Heart myeloperoxidase activity (n = 6 in each group) and (B) plasma endocan levels (n = 6 in each group) in rats treated with saline, endotoxin (10 mg/kg), endotoxin and LNAME (50 mg/kg), endotoxin and MEG sodium succinate (10 mg/kg), and endotoxin and FeTPPS (30 mg/kg). See Methods section for treatment group design. Results are expressed as mean ± SEM. *p < 0.01 compared with control; #p < 0.01 compared with endotoxin-treated rats. Abbreviations as in Figure 1.
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Figure 5 Leukocyte behavior in the mesentery venules of rats treated with saline, endotoxin (10 mg/kg), endotoxin and LNAME (50 mg/kg), endotoxin and MEG sodium succinate (10 mg/kg), and endotoxin and FeTPPS (30 mg/kg). See Methods section for treatment group design. Results are expressed as mean ± SEM (n = 6 in each group). *p < 0.01 compared with control; #p < 0.01 compared with endotoxin-treated rats. Abbreviations as in Figure 1.
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Figure 6 Effects of L-NAME (50 mg/kg), MEG sodium succinate (10 mg/kg), and FeTPPS (30 mg/kg) on endotoxin-induced heart inducible nitric oxide synthase (iNOS) protein expression and plasma nitrite/nitrate levels. See Methods section for treatment group design. (A) Heart iNOS protein expression (n = 6 in each group). Semiquantitative analysis was performed on the basis of relative I-kappa-B/G3PDH density. (B) Plasma nitrite/nitrate levels (n = 6 in each group). Results are expressed as mean ± SEM. *p < 0.01 compared with control; #p < 0.01 compared with endotoxin-treated rats. Abbreviations as in Figure 1.
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