Biphasic intraocular pressure response to calcitonin gene-related peptide

Abstract

PURPOSE. To examine the effects of calcitonin gene-related peptide (CGRP) on intraocular pressure (IOP). METHODS. IOP was periodically measured in rabbits treated with intravitreal injection (20 æl) of either: 1) CGRP (10 -4 ~ 10 -7 M) into one eye; 2) CGRP (10 -4 or 10 -6 M) into both eyes 30 min after intravitreal administration of CGRP-(8–37) (10 -3 M), a CGRP1 receptor antagonist, into one eye; 3) CGRP (10 -4 or 10 -6 M) into one eye 30 min after intravenous administration (200 mg/kg) of either Nw-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of nitric oxide synthase (NOS), or aminoguanidine (AG), a selective inhibitor of inducible NOS; or 4) CGRP (10 -4 or 10 -6 M) into one eye along with intraperitoneal indomethacin (50 mg/ kg at –1 and 4 h). RESULTS. CGRP (10 -4 and 10 -5 M) produced a biphasic IOP response, which consisted of an early ocular hypertensive phase and a subsequent sustained hypotensive phase. While CGRP (10 -6 M) yielded only a profound IOP reduction. CGRP-(8–37) significantly inhibited the IOP elevation induced by CGRP (10 -4 M) and completely abolished the IOP reduction induced by CGRP (10 -6 M). The IOP increase induced by CGRP (10 -4 M) was completely abolished by L-NAME, but not affected by AG. The IOP reduction induced by CGRP (10 -6 M) was not affected by L-NAME. Indomethacin did not significantly affect the IOP responses to CGRP. CONCLUSIONS. CGRP dose-dependently produces a biphasic IOP response, which is mediated by CGRP1 receptors. It is suggested that constitutive NOS is involved in the early ocular hypertensive response.