The ocular hypotensive effect of the ETB receptor selective agonist, sarafotoxin S6c, in rabbits.
OBJECTIVE
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.


CONCLUSIONS
STX-S6c reduces the IOP in rabbits in a dose-dependent fashion, presumably mediated through the ETB receptors.
Haque
M S
MS
Department of Ophthalmology, Gifu University School of Medicine, Japan.
Taniguchi
T
T
Sugiyama
K
K
Okada
K
K
Kitazawa
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001082:Aqueous Humor; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000737:chemistry / Q000494:pharmacology; D005136:Eye Proteins / Q000032:analysis; D005260:Female; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D015814:Ocular Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D011817:Rabbits; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000737:chemistry / Q000494:pharmacology*
D016232:Endothelins; D005136:Eye Proteins; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6