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Effects of manganese tetrakis (4‐N‐methylpyridyl) porphyrin (MnTMPyP) on dexmedetomidine‐induced contractions in the aorta of normal and septic rats
Author(s) -
Manio Michael Magtoto,
Vanhoutte Paul M,
Man Ricky Y.K.,
Ng Jacobus KF
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb596
Subject(s) - dexmedetomidine , chemistry , peroxynitrite , in vivo , pharmacology , lipopolysaccharide , aorta , ex vivo , saline , anesthesia , medicine , biochemistry , in vitro , biology , superoxide , microbiology and biotechnology , sedation , enzyme
Study Objective The aim of the present study was to investigate the effects of peroxynitrite scavenging on dexmedetomidine‐induced contractions of the rat aorta after acute in vivo exposure to lipopolysaccharide. (LPS) Methodology Male SD rats (eight to ten weeks old) were injected intraperitoneally with (1mg/kg) of LPS or normal saline. Two hours later, their aortas were harvested. Aortic rings were suspended for isometric tension recording in organ chambers and incubated with vehicle, L‐NAME (100 uM), indomethacin (10 uM), 1400W (10uM), and the peroxynitrite decomposition catalyst manganese tetrakis (4‐N‐methylpyridyl) porphyrin (MnTMPyP) (10uM). Concentration‐contraction curves to dexmedetomidine (10nM to 10uM) were obtained. Plasma cytokine concentrations were measured before and after the administration of LPS. The expression of iNOS and 3‐nitrotyrosine were measured using immunofluorescence and Western blotting. Results LPS treatment attenuated dexmedetomidine‐induced contractions after acute in vivo exposure to LPS and in the presence of MnTMPyP and 1400W, in aortic rings without endothelium. TNF‐á and IL‐6 were increased after 2 hours of LPS. Conclusion These data indicate that LPS attenuates the contractile responses to dexmedetomidine and ex vivo treatment with MnTMPyP and 1400W. Circulating endotoxin induces the release of the cytokines TNF‐á and IL‐6 after two hours.