THE OCULAR HYPOTENSIVE EFFECT OF THE ETB RECEPTOR-SELECTIVE AGONIST, SARAFOTOXIN S6C, IN RABBITS

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 var ious doses of STX-S6c. Methods. Each concentration (10(-4) to 10(-7) M ) of STX-S6c was injected intravitreally (20 mu l/eye) into one eye. T he contralateral eye of each was used as a control. The IOP was measur ed periodically using a calibrated pneumatonometer. Indomethacin (50 m g kg(-1)) or vehicle (10 ml kg(-1); 0.05 M phosphate buffer) was admin istered intraperitoneally twice, before and after intravitreal injecti on of STX-S6c (10(-5) M), and IOP was measured in the same protocol fo r 24 hours. Results. In the STX-S6c (10(-4) and 10(-5) M) group, the I OP 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 al so resulted in significant reduction of IOP observed from 24 to 72 hou rs 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 s ignificant correlation with the doses of STX-S6c (r = -0.856; P = 0.00 01) 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 rece ived higher doses of STX-S6c. Conclusion. STX-S6c reduces the IOP in r abbits in a dose-dependent fashion, presumably mediated through the ET B receptors.