title: Role of endothelium-derived hyperpolarizing factor in phenylephrine-induced oscillatory vasomotion in rat small mesenteric artery.
abstract: BACKGROUND
  In small mesenteric arteries, endothelium-derived hyperpolarizing factor (EDHF) in addition to endothelium-derived relaxing factors (EDRFs) including NO plays an important role in acetylcholine-induced vasodilation. It has been reported that EDRFs play an important role in alpha(1)-adrenoceptor agonist-induced oscillatory vasomotion and in limiting vasoconstrictor response to the agonists; however, contribution of EDHF to the alpha(1)-agonist-induced oscillation is unknown.
  
  
  METHODS
  Rat small mesenteric arteries were isolated and cannulated at each end with a glass micropipette. The vessels were immersed in a bath (37 degrees C) containing physiologic saline solution. Changes in vessel diameter were measured using an optical density video detection system.
  
  
  RESULTS
  Denudation of the endothelium and inhibition of NO synthesis caused a leftward shift in the concentration-response relation for phenylephrine in the mesenteric arteries, whereas inhibition of cyclooxygenase by indomethacin had no effect. Blockade of Ca2+-activated K+ (K(Ca)) channels by charybdotoxin and apamin caused a further leftward shift in the concentration-response relation in the vessels pretreated with Nomega-nitro-l-arginine methylester and indomethacin. Phenylephrine at concentrations higher than 10(-6) m caused endothelium-dependent oscillatory vasomotion, which was reduced but not abolished after combined inhibition of the cyclooxygenase and NO synthase pathways. However, the K(Ca) channel blockers completely abolished the remaining component of oscillation.
  
  
  CONCLUSIONS
  Endothelially-derived NO is an important modulator of sustained agonist-induced vasoconstriction. NO, as well as endothelially-derived cyclooxygenase products and EDHF, also contribute significantly to phenylephrine-induced oscillatory vasomotion.
authors.affiliation: Department of Anesthesiology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8556, Japan. kokazaki@hnh.hosp.go.jp
authors.forename: Kayoko
authors.initials: K
authors.lastname: Okazaki
authors.forename: Sumihiko
authors.initials: S
authors.lastname: Seki
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kanaya
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hattori
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Tohse
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Namiki
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D010656:Phenylephrine; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin; D007213:Indomethacin