title: Beraprost sodium, a stable prostacyclin analogue, elicits dilation of isolated porcine retinal arterioles: roles of eNOS and potassium channels.
abstract: OBJECTIVE
  Prostacyclin (PGI2) is usually described as an endoEDRFsthelium-derived relaxing factor, but the vasoreactivity to PGI2 in the retinal arterioles and the underlying mechanisms are not fully understood. We examined the effects of PGI2 on the retinal microcirculation using beraprost sodium (BPS), a stable PGI2 analogue, and the signaling mechanisms involved in this vasomotor activity.
  
  
  METHODS
  Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to BPS.
  
  
  RESULTS
  Beraprost sodium elicited dose-dependent (0.1 pM-0.1 μM) vasodilation of the retinal arterioles that was abolished by the PGI2 receptor (IP) antagonist CAY10441. Beraprost sodium-induced vasodilation decreased by 50% after the endothelium was removed and was inhibited by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) comparable with denudation. Inhibition of soluble guanylyl cyclase by 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and blockage of protein kinase A (PKA) by Rp-8-Br-cAMPS were comparable to L-NAME. Beraprost sodium-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium, and the adenosine triphosphate-sensitive potassium (KATP) channel blocker, glibenclamide. Residual vasodilation in the presence of glibenclamide decreased further with subsequent application of ODQ.
  
  
  CONCLUSIONS
  Beraprost sodium, a stable PGI2 analogue, causes vasodilation of the retinal arterioles mediated via the IP receptor. The current findings suggest that BPS elicits endothelium-dependent and -independent dilation of the retinal arterioles mediated by NO induced by activation of PKA in the endothelium and the KATP channel activation in the vascular smooth muscle, respectively.
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ono
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Nagaoka
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Omae
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tanano
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kamiya
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Otani
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishibazawa
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001593:Benzyl Compounds / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D044006:Receptors, Epoprostenol / Q000037:antagonists & inhibitors / Q000502:physiology; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C514222:(2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline); D001593:Benzyl Compounds; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D015221:Potassium Channels; D044006:Receptors, Epoprostenol; D014665:Vasodilator Agents; C015482:protein kinase modulator; D009569:Nitric Oxide; C048081:beraprost; D011464:Epoprostenol; D011494:Protein Kinases
keywords: beraprost sodium; nitric oxide; potassium channel; prostacyclin; vasodilation