Involvement of nitric oxide in the ocular hypotensive action of nipradilol.
OBJECTIVE
To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a beta-blocker with alpha( 1)-blocking activity.


METHODS
Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxy-PTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without c-PTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment.


RESULTS
Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1 approximately 2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows.


CONCLUSIONS
Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits.
Sugiyama
T
T
Department of Ophthalmology, Osaka Medical College, Osaka, Japan. opt017@poh.osaka-med.ac.jp
Kida
T
T
Mizuno
K
K
Kojima
S
S
Ikeda
T
T
D000287:Administration, Topical; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001082:Aqueous Humor / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D012590:Sclera / Q000378:metabolism; D014602:Uvea / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001565:Benzoates; D007093:Imidazoles; D011412:Propanolamines; D014665:Vasodilator Agents; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; C036089:nipradilol