Ocular effects of adrenomedullin

The purpose of this study was to determine the expression and effects of ad renomedullin (AM), a novel vasodilator peptide, in the eye. Expression of A M mRNA was examined in the rat iris-ciliary body using reverse transcriptio n-polymerase chain reaction (RT-PCR). In rabbits, intraocular pressure (IOP ) was measured periodically after intravitreal injection (20 mu l) of AM (1 0(-7)-10(-4) M) into one eye. in separate groups of rabbits, 30 min after I ntravitreal injection of either AM-(22-52) (10(-3) M), a specific AM recept or antagonist, or CGRP-(8-37) (10-3 M), a CGRP1 receptor antagonist, into o ne eye, AM (10(-6) M) was injected into both eyes, and IOP was measured. Us ing different rabbits, aqueous protein and cAMP concentrations were determi ned 6 hr after injection of AM. Expression of AM mRNA was detected in the r at 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 hy potensive effect of AM (10(-6) M), whereas pretreatment with AM-(22-52) com pletely abolished it. AM (10(-6) M) did not significantly affect aqueous pr otein 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-cil iary body and decreases TOP mainly via specific AM receptors, and suggest t hat AM may play a role in controlling IOP. (C) 1999 Academic Press.