title: Vasorelaxing effect of U50,488H in pulmonary artery and underlying mechanism in rats.
abstract: OBJECTIVE
  To investigate the relaxation effect and underlying mechanism of U50,488H (a selective kappa-opioid receptor agonist) in pulmonary artery in the rat.
  
  
  METHODS
  Isolated pulmonary artery ring was perfused and the tension of the vessel was measured.
  
  
  RESULTS
  U50,488H relaxed the pulmonary artery ring in a dose-dependent manner and the effect was abolished by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. The relaxation effect of U50,488H in pulmonary artery was partially endothelium-dependent and was significantly attenuated in the presence of L-NAME. The relaxation effect of U50,488H was significantly attenuated by K(V) channel blocker 4-AP (4-aminopyridine), but not by glibenclamide (ATP-sensitive K+ channel blocker) nor TEA (tetraethylamonium, Ca2+-activated K+ channel blocker). Further study also showed that endothelium denudation and 4-AP have an additive inhibitory effect on pulmonary artery relaxation caused by U50,488H.
  
  
  CONCLUSIONS
  Kappa-opioid receptor activation by U50,488H relaxes pulmonary artery via two separate pathways: one is endothelium-derived nitric oxide, the other is K(V) channel in pulmonary artery smooth muscle.
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Sai
authors.initials: S
authors.lastname: Ma
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zang
authors.forename: Shun-Yan
authors.initials: SY
authors.lastname: Lu
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Bi
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Ma
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Ma
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Pei
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists
chemical_list: D000319:Adrenergic beta-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017473:Receptors, Opioid, kappa; D009569:Nitric Oxide; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins; D001285:Atropine; D011433:Propranolol; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin