title: Effects of topically instilled bunazosin, an alpha1-adrenoceptor antagonist, on constrictions induced by phenylephrine and ET-1 in rabbit retinal arteries.
abstract: OBJECTIVE
  To examine the inhibitory effects of topically instilled bunazosin hydrochloride (bunazosin), a selective alpha1-adrenoceptor antagonist, on the retinal artery constrictions induced by intravitreous phenylephrine hydrochloride (phenylephrine) and endothelin (ET)-1 in rabbits.
  
  
  METHODS
  Phenylephrine or ET-1 (20 microL) was injected into the central part of the vitreous in both eyes in pigmented rabbits. Color fundus photographs were taken at 5 minutes before and 60 minutes after the injection. The average diameter of the major retinal arteries at the rim of the optic nerve head (ONH) was normalized with respect to ONH diameter. Bunazosin was instilled into one eye (chosen randomly) and vehicle into the fellow eye at 60 minutes before the intravitreous injection. To examine any interaction between the alpha1-adrenoceptor and ET receptor, phenylephrine and ET-1 were co-injected at individually ineffective doses. In addition, ET-1-induced vasoconstriction was examined after unilateral superior cervical ganglionectomy. The binding affinities of bunazosin for ETA and ETB receptors were also evaluated. The series of experiments was performed as masked tests.
  
  
  RESULTS
  Retinal arteries were dose-dependently constricted by both intravitreous phenylephrine and intravitreous ET-1. Topically instilled bunazosin at 0.01% partly inhibited both of these vasoconstrictions on the ipsilateral side, but not on the contralateral side. Bunazosin did not bind to ET receptors. Co-injection of phenylephrine and ET-1 at individually ineffective doses constricted retinal arteries significantly. An adrenergic supersensitivity in retinal arteries was observed after superior cervical ganglionectomy only on the ganglionectomized eye. The ET-1-induced vasoconstriction was significantly weaker in cervical ganglionectomized eyes than in sham-surgery eyes.
  
  
  CONCLUSIONS
  The present findings suggest that topically instilled bunazosin reaches the posterior retina by local penetration at concentrations sufficient to attenuate the phenylephrine- or ET-1-induced constriction of retinal arteries in normal rabbit eyes, and that the inhibitory effect of bunazosin on the ET-1-induced vasoconstriction in this tissue may be partly attributable to an interaction between the alpha1-adrenoceptor and ET receptor.
authors.affiliation: Research and Development Division, Santen Pharmaceutical Co. Ltd., Nara, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Asai
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ishii
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000287:Administration, Topical; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D019332:Endothelin-1 / Q000494:pharmacology*; D015171:Ganglionectomy; D007267:Injections; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D011799:Quinazolines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D017466:Receptors, Endothelin / Q000378:metabolism; D012161:Retinal Artery / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000502:physiology / Q000601:surgery; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014822:Vitreous Body
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004338:Drug Combinations; D019332:Endothelin-1; D011799:Quinazolines; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; C018176:bunazosin