endothelin-1 and bunazosin

To investigate the effects of bunazosin hydrochloride, an alpha1-adrenergic blocker, on the impairment of optic nerve head (ONH) blood flow and depression of visual function induced by repeated intravitreal injections of endothelin-1 (ET-1) in rabbits.. We injected ET-1 (20 pmol) into the right posterior vitreous of rabbits twice a week for 4 weeks, and the observation period was set at 8 weeks (starting the first injection). The animals that received ET01 were divided into two groups: twice a day for 8 weeks, o ne group received topical 0.01% bunazosin, while the second received the vehicle for bunazosin. The ONH blood flow was monitored using the laser speckle method, and visual function was assessed by examining visually evoked potentials (VEPs). Changes in the ONH cup/disk area and in the number of cells in the retinal ganglion cell layer (CCL) were also determined.. Repeated injections of ET-1 decreased the ONH blood flow, prolonged the VEP implicit time, enlarged the optic cup, and decreased the number of GCL cells. Topical bunazosin significantly decreased these impairments.. These results indicate that in rabbits, topical bunazosin suppresses the changes in ONH circulation and function induced by intravitreal ET-1.

Topics: Administration, Topical; Adrenergic alpha-Antagonists; Animals; Blood Pressure; Endothelin-1; Evoked Potentials, Visual; Injections; Intraocular Pressure; Ischemia; Optic Disk; Quinazolines; Rabbits; Regional Blood Flow; Retina; Vitreous Body

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.. 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.. 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.. 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.

Topics: Administration, Topical; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Dose-Response Relationship, Drug; Drug Combinations; Endothelin-1; Ganglionectomy; Injections; Male; Phenylephrine; Quinazolines; Rabbits; Receptors, Endothelin; Retinal Artery; Superior Cervical Ganglion; Vasoconstriction; Vasoconstrictor Agents; Vitreous Body