title: Intravenous morphine reduces plasma endothelin 1 concentration through activation of neutral endopeptidase 24.11 in patients with myocardial infarction.
abstract: OBJECTIVE
  Morphine has multiple cardiovascular effects, but its action on hydrolysis of endothelin 1 (ET-1) has not been investigated.
  
  
  METHODS
  We measured plasma levels of ET-1, C-terminal degradation products of ET-1, and neutral endopeptidase 24.11 (NEP) in 68 patients with acute Q-wave myocardial infarction and 29 control subjects. All the patients underwent blood sampling at initial presentation and 10 minutes later. Thirty-six of those with Q-wave myocardial infarction intravenously received 3 mg of morphine immediately after the first sampling (group 1), and the other 32 received the same after the second sampling (group 2). Twenty-four of the control subjects (group 3) were randomized to the protocol of group 1, and the remaining 5 subjects (group 4) were randomized to the protocol of group 2.
  
  
  RESULTS
  The plasma ET-1 levels were significantly higher in groups 1 and 2 than in groups 3 and 4 (control groups). In group 1, the ET-1 level decreased significantly at second blood samplings (2.5+/-0.4 pmol/L versus 1.7+/-0.6 pmol/L, P <.001), whereas there were no definite changes of ET-1 levels in group 2 (2.5+/-0.5 pmol/L versus 2.6+/-0.6 pmol/L, P =not significant). However, the C-terminal degradation products increased significantly at second blood samplings in group 1 (0.8+/-0.2 pmol/L versus 1.3+/-0.4 pmol/L, P <.001), whereas there were no definite changes in group 2 (0.9+/-0.3 pmol/L versus 0.9+/-0.4 pmol/L, P =not significant). There was no significant difference in baseline NEP activities between groups 1 and 2 (5.02+/-1.30 nmol/mg protein versus 5.06+/-1.48 nmol/mg protein, P =not significant). However, the NEP activities at second blood samplings declined significantly in group 1 (9.76+/-1.76 nmol/mg protein, P <.001 versus baseline), whereas no definite changes were observed in group 2 (5.09+/-1.62 nmol/mg protein, P =not significant versus baseline).
  
  
  CONCLUSIONS
  Intravenous morphine may increase NEP activities to accentuate hydrolysis of ET-1.
authors.affiliation: Department of Emergency Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: T L
authors.initials: TL
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Chang
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D016903:Drug Monitoring; D004638:Emergency Treatment / Q000379:methods; D019332:Endothelin-1 / Q000097:blood* / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D015260:Neprilysin / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D019332:Endothelin-1; D009020:Morphine; D003402:Creatine Kinase; D015260:Neprilysin