Adrenomedullin and ocular inflammation in the rabbit

Adrenomedullin administered peripherally in the rabbit (at doses of 1.25, 2.5 and 5 microg/kg ) caused a dose-dependent conjunctival hyperemia accompanied by an increase of inflammatory cell number and prostaglandin E(2) concentration in the aqueous humor, and of uveal vascular response and myeloperoxidase activity. The inflammatory effect of the peptide, injected at the dose of 5 microg/kg, was abolished by pretreatment with the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methylester (50 mg/kg, i.v.). Moreover, the i.v. pretreatment with the calcitonin gene-related peptide 8-37 fragment (calcitonin gene-related peptide, CGRP-(8-37), 2.5 microg/kg), receptor antagonist of CGRP, did not inhibit the conjunctival hyperemia. In contrast, the i.v. pretreatment with the adrenomedullin receptor antagonist, adrenomedullin-(22-52) fragment (2.5 microg/kg), abolished adrenomedullin-induced ocular inflammation. These results suggest that adrenomedullin causes conjunctival hyperemia, and this effect involves the nitric oxide system acting through specific adrenomedullin receptors.