Effects of topically instilled bunazosin hydrochloride and other ocular hypotensive drugs on endothelin-1-induced constriction in rabbit retinal arteries.
OBJECTIVE
To compare the inhibitory effect of topically instilled bunazosin hydrochloride (bunazosin), a selective alpha(1)-adrenoceptor antagonist, on the endothelin (ET)-1-induced vasoconstriction in rabbit retinal arteries with the effects of other ocular hypotensive drugs.


METHODS
ET-1 was injected into the central part of the vitreous of both eyes of pigmented rabbits. Color fundus photographs were taken 5 min before and 60 min after the injection. The average diameters of the two major retinal arteries at the rim of the optic nerve head (ONH) were normalized with respect to ONH diameter. Fifty microliters of 0.01% bunazosin, or 0.12% isopropyl unoprostone (unoprostone), 1% dorzolamide hydrochloride (dorzolamide), 0.25% nipradilol, 0.5% betaxolol hydrochloride (betaxolol), or 0.5% timolol maleate (timolol) was instilled into one eye of each rabbit 60 min before the ET-1 injection. The series of experiments was performed as masked tests.


RESULTS
Bunazosin and unoprostone inhibited the ET-1-induced constriction of retinal arteries by 103% (P = 0.012 versus contralateral eyes) and 50% (P = 0.037), respectively. Dorzolamide, nipradilol, betaxolol, and timolol had no significant effects in this experiment.


CONCLUSIONS
Under our experimental conditions, bunazosin and unoprostone inhibited the ET-1-induced constriction. Hence, bunazosin and unoprostone may be clinically more effective against ET-1-related retinal diseases.
Okada
Yuji
Y
Research and Development Center, Santen Pharmaceutical Company, Ltd., Nara, Ikoma 630-0101, Japan. yuji.okada@santen.co.jp.
Ichikawa
Masaki
M
Ishii
Kiyoshi
K
Hara
Hideaki
H
D000287:Administration, Topical; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D011799:Quinazolines / Q000008:administration & dosage*; D011817:Rabbits; D012161:Retinal Artery / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D019332:Endothelin-1; D011799:Quinazolines; C018176:bunazosin