title: Morphine, opioids, and the feline pulmonary vascular bed.
abstract: BACKGROUND
  Opioid-induced vasodepressor responses have been reported in a variety of species and laboratory models. The aim of this study was to ascertain the relative potencies of different clinically relevant opioids compared with traditional vasodepressor agents in the feline pulmonary vascular bed. A second aim was to study the effects of morphine and to identify the receptors involved in the mediation or the modulation of these effects.
  
  
  METHODS
  This was a prospective vehicle-controlled study involving an intact chest preparation of adult mongrel cats. The effects of various opioids, morphine, fentanyl, remifentanil, sufentanil, and meperidine were compared with other vasodepressor agents. Additionally, the effects of L-N(5)-(1-iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide [selective cyclooxygenase (COX)-2 inhibitor], glibenclamide (ATP-sensitive K+ channel blocker), naloxone (non-selective opioid receptor antagonist), and diphenhydramine (histamine H(1)-receptor antagonist) were investigated on pulmonary arterial responses to morphine and other selected agonists in the feline pulmonary vascular bed. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded.
  
  
  RESULTS
  In the cat pulmonary vascular bed of the isolated left lower lobe, morphine, remifentanil, fentanyl, sufentanil, and meperidine induced a dose-dependent moderate vasodepressor response and it appeared that sufentanil was the most potent on a nanomolar basis. The effects of morphine were not significantly altered after administration of L-NIO, nimesulide, and glibenclamide. However, the vascular responses to morphine were significantly attenuated following administration of naloxone and diphenhydramine.
  
  
  CONCLUSIONS
  The results of the present study suggest that sufentanil appears to have slightly more potency and morphine the least of the five opioid agonists studied on a nanomolar basis. Morphine-induced vasodilatory responses appeared to be mediated or modulated by both opioid receptor and histamine-receptor-sensitive pathways.
authors.affiliation: Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. akaye@lsuhsc.edu
authors.forename: A D
authors.initials: AD
authors.lastname: Kaye
authors.forename: J M
authors.initials: JM
authors.lastname: Hoover
authors.forename: A J
authors.initials: AJ
authors.lastname: Kaye
authors.forename: I N
authors.initials: IN
authors.lastname: Ibrahim
authors.forename: C
authors.initials: C
authors.lastname: Fox
authors.forename: A
authors.initials: A
authors.lastname: Bajwa
authors.forename: M
authors.initials: M
authors.lastname: Anwar
authors.forename: A M
authors.initials: AM
authors.lastname: Fields
authors.forename: A
authors.initials: A
authors.lastname: Baluch
authors.forename: S
authors.initials: S
authors.lastname: Huffman
authors.forename: W
authors.initials: W
authors.lastname: Chilian
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004155:Diphenhydramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005283:Fentanyl / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008614:Meperidine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects; D000077208:Remifentanil; D017409:Sufentanil / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D013449:Sulfonamides; D014665:Vasodilator Agents; C065027:N(G)-iminoethylornithine; D009270:Naloxone; D009020:Morphine; D004155:Diphenhydramine; D008614:Meperidine; D017409:Sufentanil; D009952:Ornithine; D000077208:Remifentanil; D005905:Glyburide; D005283:Fentanyl; C012655:nimesulide