title: Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles.
abstract: OBJECTIVE
  Endothelial dysfunction and impaired vasodilation may be involved in the pathogenesis of retinal vascular diseases. In the present study, the mechanisms underlying bradykinin vasodilation were examined and whether calcium-activated potassium channels of small (SK(Ca)) and intermediate (IK(Ca)) conductance are involved in regulation of endothelium-dependent vasodilation in retinal arterioles was investigated.
  
  
  METHODS
  Porcine retinal arterioles (diameter approximately 112 microm, N = 119) were mounted in microvascular myographs for isometric tension recordings. The arterioles were contracted with the thromboxane analogue, U46619, and concentration-response curves were constructed for bradykinin and a novel opener of SK(Ca) and IK(Ca) channels, NS309.
  
  
  RESULTS
  In U46619-contracted arterioles, bradykinin and NS309 induced concentration-dependent relaxations. In vessels without endothelium, bradykinin relaxation was abolished and NS309 relaxation was attenuated. Inhibition of NO synthase with asymmetric dimethylarginine and/or cyclooxygenase with indomethacin markedly reduced bradykinin and NS309 relaxation. NO synthase and cyclooxygenase inhibition together with oxyhemoglobin abolished bradykinin relaxation and attenuated NS309 relaxation. Blocking of SK(Ca) and IK(Ca) channels with apamin plus charybdotoxin or blocking of SK(Ca) channels alone in the absence and the presence of indomethacin markedly reduced bradykinin and NS309 relaxation, whereas blocking of IK(Ca) channels had no significant effect. In vessels without endothelium, blocking of SK(Ca) channels alone had no effect on sodium nitroprusside-induced relaxation.
  
  
  CONCLUSIONS
  In porcine retinal arterioles, NO and prostaglandins mediate endothelium-dependent relaxation to bradykinin and NS309. Moreover, these findings suggest that SK(Ca) channels contribute to NO-mediated relaxation induced by bradykinin and NS309 and, hence, may play an important role in retinal arterial endothelial function.
authors.affiliation: Department of Pharmacology, Aarhus University, Aarhus C, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dalsgaard
authors.forename: Christel
authors.initials: C
authors.lastname: Kroigaard
authors.forename: Toke
authors.initials: T
authors.lastname: Bek
authors.forename: Ulf
authors.initials: U
authors.lastname: Simonsen
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D010091:Oximes / Q000494:pharmacology; D012161:Retinal Artery / Q000502:physiology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D010091:Oximes; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C487735:dimethylarginine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D001920:Bradykinin; D007213:Indomethacin