Adrenomedullin and ocular inflammation in the rabbit

Adrenomedullin administered peripherally in the rabbit (at doses of 1.25, 2 .5 and 5 mu g/kg) caused a dose-dependent conjunctival hyperemia accompanie d by an increase of inflammatory cell number and prostaglandin E-2 concentr ation in the aqueous humor, and of uveal vascular response and myeloperoxid ase activity. The inflammatory effect of the peptide, injected at the dose of 5 mu g/kg, was abolished by pretreatment with the inhibitor of nitric ox ide 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 fragmen t (calcitonin gene-related peptide, CGRP-(8-37), 2.5 mu g/kg), receptor ant agonist of CGRP, did not inhibit the conjunctival hyperemia. In contrast, t he i.v. pretreatment with the adrenomedullin receptor antagonist, adrenomed uilin-(22-52) fragment (2.5 mu g/kg), abolished adrenomedullin-induced ocul ar inflammation. These results suggest that adrenomedullin causes conjuncti val hyperemia, and this effect involves the nitric oxide system acting thro ugh specific adrenomedullin receptors. (C) 2000 Elsevier Science B.V. All r ights reserved.