The effect of angiotensin II on uveoscleral outflow in rabbits.
OBJECTIVE
In our previous study, we showed that the AT1 receptor antagonist increased uveoscleral outflow (USF) when topically applied to the rabbit eye. However this increase was too small to demonstrate a clear physiological role for ocular angiotensin II (AII). Hence, the purpose of this study was to determine whether ocular AII influenced USF regulation, and if so, how this occurred.


METHODS
USF was measured by the FITC-dextran perfusion method in albino rabbits. AII and its receptor antagonists were directly applied into the anterior chamber by adding into the perfusate and by perfusing with FITC-dextran. We also analyzed angiotensin receptors on the rabbit ciliary body membrane by a receptor binding assay with 125I-[Sar1), Ile8]-AII as a ligand.


RESULTS
CS-088 (1 microg/ml) increased USF by 24% while AII decreased USF in a concentration-dependent manner between 10 and 500 nM. Its maximum decrease of 19% occurred at 500 nM. At this AII concentration the USF reduction was antagonized by 1 microg/ml CS-088, an AT1-receptor antagonist, but not by the same concentration of PD-123,177, an AT2-receptor antagonist. Specific 125I-[Sar1, Ile8]-AII binding to the rabbit ciliary body membranes was inhibited by CS-088 with an inhibition constant of 7.05 nM, whereas inhibition by PD-123,177 was not observed.


CONCLUSIONS
Ocular AII was indicated to attenuate USF via AT1 receptors in rabbits, however its physiological effect was not critical in IOP regulation.
Inoue
T
T
Research Laboratories of Neuroscience and Immunology, Sankyo Company Limited, Tokyo, Japan. inotat@shina.sankyo.co.jp
Yokoyoma
T
T
Koike
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D001082:Aqueous Humor / Q000378:metabolism*; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism; D012590:Sclera / Q000187:drug effects* / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D003911:Dextrans; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C015219:fluorescein isothiocyanate dextran; D000804:Angiotensin II; C066253:PD 123177; C437965:olmesartan; D016650:Fluorescein-5-isothiocyanate