title: Characteristics of ACh-induced hyperpolarization and relaxation in rabbit jugular vein.
abstract: OBJECTIVE
  The roles played by endothelium-derived NO and prostacyclin and by endothelial cell hyperpolarization in ACh-induced relaxation have been well characterized in arteries. However, the mechanisms underlying ACh-induced relaxation in veins remain to be fully clarified.
  
  
  METHODS
  ACh-induced smooth muscle cell (SMC) hyperpolarization and relaxation were measured in endothelium-intact and -denuded preparations of rabbit jugular vein.
  
  
  RESULTS
  In endothelium-intact preparations, ACh (≤ 10⁻⁸ M) marginally increased the intracellular concentration of Ca²⁺ ([Ca²⁺](i)) in endothelial cells but did not alter the SMC membrane potential. However, ACh (10⁻¹⁰ -10⁻⁸ M) induced a concentration-dependent relaxation during the contraction induced by PGF(2α) and this relaxation was blocked by the NO synthase inhibitor N(ω) -nitro-l-arginine. ACh (10⁻⁸ -10⁻⁶ M) concentration-dependently increased endothelial [Ca²⁺](i) and induced SMC hyperpolarization and relaxation. These SMC responses were blocked in the combined presence of apamin [blocker of small-conductance Ca²⁺-activated K⁺ (SK(Ca) , K(Ca) 2.3) channel], TRAM 34 [blocker of intermediate-conductance Ca²⁺ -activated K⁺ (IK(Ca) , K(Ca) 3.1) channel] and margatoxin [blocker of subfamily of voltage-gated K⁺ (K(V) ) channel, K(V) 1].
  
  
  CONCLUSIONS
  In rabbit jugular vein, NO plays a primary role in endothelium-dependent relaxation at very low concentrations of ACh (10⁻¹⁰ -10⁻⁸ M). At higher concentrations, ACh (10⁻⁸ -3 × 10⁻⁶ M) induces SMC hyperpolarization through activation of endothelial IK(Ca) , K(V) 1 and (possibly) SK(Ca) channels and produces relaxation. These results imply that ACh regulates rabbit jugular vein tonus through activation of two endothelium-dependent regulatory mechanisms.
authors.affiliation: Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Japan. titoh@med.nagoya-cu.ac.jp
authors.forename: Takeo
authors.initials: T
authors.lastname: Itoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Maekawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shibayama
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D007601:Jugular Veins / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000109:Acetylcholine; D002118:Calcium