Amelioration by topical bunazosin hydrochloride of the impairment in ocular blood flow caused by nitric oxide synthase inhibition in rabbits.
We investigated whether topical instillation of an alpha(1)-adrenergic blocker would improve an insufficient blood supply in the optic nerve head (ONH) and visual function, in rabbits. The effect of systemic NOS inhibition on visual-evoked potentials (VEPs) and hemodynamics in ONH were determined. VEPs were recorded before and every 15 min during a 120-min observation period after an intravenous injection of 50 mg/kg N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Capillary blood flow in ONH was evaluated by the laser speckle method throughout the same period. Then, we investigated the effect of topical instillation of a recently developed alpha(1) adrenergic blocker, bunazosin hydrochloride (0.01%), 60 min prior to the intravenous L-NAME (50 mg/kg) on the changes by NOS inhibition. The VEP amplitudes were reduced by L-NAME (10, 20, and 50 mg/kg) in a dose-dependent manner, while the VEP implicit time was unchanged, and no significant changes were detected in the electroretinogram. The reductions in ONH capillary blood flow and VEP amplitudes caused by L-NAME (50 mg/kg) were significantly suppressed by an instillation of bunazosin hydrochloride. These results indicate that blocking alpha(1)-adrenergic receptors may ameliorate the impairments in blood flow and retinal function caused by NOS inhibition. The enhancement of basal vascular tone due to deprivation of continuous NO production may be diminished by this alpha(1)-adrenergic blocker.
Goto
Wakana
W
Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-cho Takatsuki Osaka, 569-8686 Japan.
Oku
Hidehiro
H
Okuno
Takashi
T
Sugiyama
Tetsuya
T
Ikeda
Tsunehiko
T
D000287:Administration, Topical; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005654:Fundus Oculi; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009898:Optic Disk / Q000098:blood supply*; D011799:Quinazolines / Q000008:administration & dosage*; D011817:Rabbits; D011930:Reaction Time / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014785:Vision, Ocular / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D011799:Quinazolines; C018176:bunazosin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester