title: Activation of cardiac endothelium as a compensatory component in endotoxin-induced cardiomyopathy: role of endothelin, prostaglandins, and nitric oxide.
abstract: BACKGROUND
  In view of growing evidence of an important endothelial paracrine regulation of cardiac function, the present study investigated the role of cardiac endothelium-derived endothelin-1 (ET-1), prostaglandins, and nitric oxide (NO) during endotoxin-induced cardiomyopathy in rabbits.
  
  
  RESULTS
  Immunohistochemical studies showed a marked transient coinduction of the inducible isoforms of NO synthase (NOS-2) and cyclooxygenase (COX-2) in endocardial endothelium and coronary arteriolar endothelium of hearts 12 hours after intravenous administration of lipopolysaccharide (LPS+12h); staining for both isoforms was much weaker 24 hours later (LPS+36h). Nitrotyrosine localization was similar to that of NOS-2, suggesting a NOS-2-related endothelial formation of peroxynitrite in septic hearts. Contractile performance of papillary muscles was depressed in both LPS-treated groups. In the LPS+12h group, however, isometric twitches were significantly prolonged (482+/-14 versus 420+/-14 ms in the saline-treated group, P<0.005). This twitch prolongation was completely reversed by simultaneous administration of BQ-123 and indomethacin to block endogenous ET-1 and prostaglandins, respectively. In addition, in the LPS+12h group, myocardial inotropic responsiveness to exogenous ET-1 was enhanced (P<0.01).
  
  
  CONCLUSIONS
  Cardiac endothelial activation and myocardial sensitization to endothelium-derived mediators may be part of an adaptive response in the early (12 hours) stages of septic cardiomyopathy.
authors.affiliation: Laboratoire d'Anesthöesiologie, Döepartement d'Anesthöesie-Röeanimation, INSERM U127, Paris, France. alexandre.mebazaa@lrb.ap-hop-paris.fr
authors.forename: A
authors.initials: A
authors.lastname: Mebazaa
authors.forename: G W
authors.initials: GW
authors.lastname: De Keulenaer
authors.forename: X
authors.initials: X
authors.lastname: Paqueron
authors.forename: L J
authors.initials: LJ
authors.lastname: Andries
authors.forename: P
authors.initials: P
authors.lastname: Ratajczak
authors.forename: S
authors.initials: S
authors.lastname: Lanone
authors.forename: C
authors.initials: C
authors.lastname: Frelin
authors.forename: D
authors.initials: D
authors.lastname: Longrois
authors.forename: D
authors.initials: D
authors.lastname: Payen
authors.forename: D L
authors.initials: DL
authors.lastname: Brutsaert
authors.forename: S U
authors.initials: SU
authors.lastname: Sys
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001667:Binding, Competitive; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood / Q000494:pharmacology; D016232:Endothelins / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology; D011817:Rabbits; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D011453:Prostaglandins; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase