The effect of topical CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure and aqueous humor dynamics in rabbits.
OBJECTIVE
To evaluate the ocular hypotensive effect of topical CS-088, an angiotensin AT1 receptor antagonist, and the effect of CS-088 on aqueous humor dynamics.


METHODS
The effects of CS-088 on intraocular pressure (IOP) were studied in 2 models of rabbit ocular hypertension. Experimental ocular hypertension was induced in albino rabbits by injecting alpha-chymotrypsin into the anterior chamber (alpha-chymotrypsin rabbit). The effects of the single application of CS-088 were examined. Additionally, CS-088 was repeatedly administered over a period of 3 weeks to hereditary ocular hypertensive rabbits (buphthalmic rabbits, JWHR bu/bu) and the IOPs were monitored throughout the experiment. The effects of CS-088 on aqueous humor dynamics were also examined in normal rabbits. In this study, the methods of IOP recovery rate, two-level constant pressure perfusion and fluorescein-dextran perfusion were used respectively to determine the aqueous inflow, outflow facility and uveoscleral outflow (USF).


RESULTS
CS-088 at 1% and 2% significantly lowered the IOP in the alpha-chymotrypsin rabbits with a maximum IOP reduction of 10.1 mmHg. The maximum effect obtained with 2% CS-088 was no greater than that with 1% CS-088. In the buphthalmic rabbits, 2% CS-088 also lowered IOP significantly. Timolol was effective in both models. In the study on aqueous humor dynamics, a slight increase in USF (17%) was seen after a topical application of CS-088 whereas changes in aqueous inflow or outflow facility were not observed.


CONCLUSIONS
Topical CS-088 can decrease IOP in rabbits. Despite the USF change, the ocular hypotensive mechanism by CS-088 was not fully determined.
Inoue
T
T
Research Laboratories of Neuroscience and Immunology, Sankyo Company Limited, Tokyo, Japan. inotat@shina.sankyo.co.jp
Yokoyoma
T
T
Mori
Y
Y
Sasaki
Y
Y
Hosokawa
T
T
Yanagisawa
H
H
Koike
H
H
D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002918:Chymotrypsin; D004195:Disease Models, Animal; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000378:metabolism; D009883:Ophthalmic Solutions; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013999:Timolol / Q000008:administration & dosage / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D009883:Ophthalmic Solutions; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D013999:Timolol; C437965:olmesartan; D002918:Chymotrypsin; C117608:alpha-chymotrypsin