Investigative ophthalmology & visual science · 1995
The ocular hypotensive effect of the ETB receptor selective agonist, sarafotoxin S6c, in rabbits.
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Haque M S, Taniguchi T, Sugiyama K, Okada K, Kitazawa Y
Аннотация
PURPOSE: Endothelin-1 (ET-1) is known to affect intraocular pressure (IOP) in rabbits, and the IOP response is likely to be mediated by the receptors ETA, ETB, or both. Sarafotoxin S6c (STX-S6c) is a selective agonist to ETB receptors. The authors attempted to clarify the role of ETB receptors in changes in IOP induced by ET-1 in rabbits using STX-S6c and to determine the relationship between the IOP response and various doses of STX-S6c.
METHODS: Each concentration (10(-4) to 10(-7) M) of STX-S6c was injected intravitreally (20 microliters/eye) into one eye. The contralateral eye of each was used as a control. The IOP was measured periodically using a calibrated pneumatonometer. Indomethacin (50 mg kg-1) or vehicle (10 ml kg-1; 0.05 M phosphate buffer) was administered intraperitoneally twice, before and after intravitreal injection of STX-S6c (10(-5) M), and IOP was measured in the same protocol for 24 hours.
RESULTS: In the STX-S6c (10(-4) and 10(-5) M) group, the IOP reduction was significant compared with the baseline (P < 0.05 to P < 0.01), starting from 6 and 4 hours and continuing until 192 and 72 hours after injection, respectively. A solution of 10(-6) M STX-S6c also resulted in significant reduction of IOP observed from 24 to 72 hours after injection (P < 0.05). The 10(-7) M solution of STX-S6c failed to affect IOP. The area under the curve of IOP response exhibited a significant correlation with the doses of STX-S6c (r = -0.856; P = 0.0001) in the treated eyes. Treatment with indomethacin failed to affect the IOP reduction caused by STX-S6c (10(-5) M). Ciliary injection and some dilatation of the iridial vessels were observed in eyes that received higher doses of STX-S6c.
CONCLUSION: STX-S6c reduces the IOP in rabbits in a dose-dependent fashion, presumably mediated through the ETB receptors.
METHODS: Each concentration (10(-4) to 10(-7) M) of STX-S6c was injected intravitreally (20 microliters/eye) into one eye. The contralateral eye of each was used as a control. The IOP was measured periodically using a calibrated pneumatonometer. Indomethacin (50 mg kg-1) or vehicle (10 ml kg-1; 0.05 M phosphate buffer) was administered intraperitoneally twice, before and after intravitreal injection of STX-S6c (10(-5) M), and IOP was measured in the same protocol for 24 hours.
RESULTS: In the STX-S6c (10(-4) and 10(-5) M) group, the IOP reduction was significant compared with the baseline (P < 0.05 to P < 0.01), starting from 6 and 4 hours and continuing until 192 and 72 hours after injection, respectively. A solution of 10(-6) M STX-S6c also resulted in significant reduction of IOP observed from 24 to 72 hours after injection (P < 0.05). The 10(-7) M solution of STX-S6c failed to affect IOP. The area under the curve of IOP response exhibited a significant correlation with the doses of STX-S6c (r = -0.856; P = 0.0001) in the treated eyes. Treatment with indomethacin failed to affect the IOP reduction caused by STX-S6c (10(-5) M). Ciliary injection and some dilatation of the iridial vessels were observed in eyes that received higher doses of STX-S6c.
CONCLUSION: STX-S6c reduces the IOP in rabbits in a dose-dependent fashion, presumably mediated through the ETB receptors.