The purpose of this study was to determine the expression and effects of adrenomedullin (AM), a novel vasodilator peptide, in the eye. Expression of AM mRNA was examined in the rat iris-ciliary body using reverse transcription-polymerase chain reaction (RT-PCR). In rabbits, intraocular pressure (IOP) was measured periodically after intravitreal injection (20 microl) of AM (10(-7)-10(-4)m) into one eye. In separate groups of rabbits, 30 min after intravitreal injection of either AM-(22-52) (10(-3)m), a specific AM receptor antagonist, or CGRP-(8-37) (10(-3)m), a CGRP1 receptor antagonist, into one eye, AM (10(-6)m) was injected into both eyes, and IOP was measured. Using different rabbits, aqueous protein and cAMP concentrations were determined 6 hr after injection of AM. Expression of AM mRNA was detected in the rat iris-ciliary body. In rabbits, intravitreally administered AM (10(-6)-10(-4)m) profoundly lowered IOP, and the maximum effect was observed at 4-8 h. The ocular hypotensive effect of AM was dose-dependent (10(-7)-10(-4)m). Pretreatment with CGRP-(8-37) did not significantly inhibit the ocular hypotensive effect of AM (10(-6)m), whereas pretreatment with AM-(22-52) completely abolished it. AM (10(-6)m) did not significantly affect aqueous protein concentration. The higher dose of AM (10(-5)m) induced a significant increase in aqueous protein, which was not associated with an increase in the aqueous cAMP content and was significantly inhibited by AM-(22-52) and CGRP-(8-37). These results demonstrate that AM is expressed in the iris-ciliary body and decreases IOP mainly via specific AM receptors, and suggest that AM may play a role in controlling IOP.
Copyright 1999 Academic Press.