ROLE OF NITRIC-OXIDE (NO) IN OCULAR INFLAMMATION

1 The actions of nitric oxide (NO) have been investigated in the rabbit eye, with particular emphasis on the relationship between NO and C-fibres and on those effects of NO that may be of importance in the inflammatory response to C-fibre stimulation. 2 The NO synthase inhibitor, N-G-nitro-L-arginine (L-NAME; 10-200 mg kg(-1)), but not the inactive analogue D-NAME (200 mg kg(-1)), was found to block the inflammatory response induced by infrared irradiation of the iris in a dose-dependent manner. The inhibitory effects of L-NAME (200 mg kg(-1)) were partially reversed by L-arginine (500 mg kg(-1)), but not by D-arginine (500 mg kg(-1)). 3 L-NAME (200 mg kg(-1)) virtually abolished the ocular effects of intravitreal injection of calcitonin gene-related peptide (CGRP) (0.3 nmol). 4 The concentration of CGRP in aqueous humour from untreated rabbit eyes was 0.1 +/- 0.001 nmol 1(-1). Irradiation of the iris raised the CORP concentration to 8.9 +/- 1.5 nmol 1(-1). L-NAME (200 mg kg(-1)) greatly suppressed the irradiation-evoked release of CGRP, the concentration in the aqueous humour being 1.2 +/- 0.2 nmol 1(-1) (P < 0.001). L-Arginine reversed the L-NAME-induced inhibition of release of CGRP, the concentration of CGRP in the aqueous humour being 9.7 +/- 0.6 nmol 1(-1). 5 In addition, a NO donor, sodium nitroprusside (0.9 mu mol), was found to raise the concentration of CGRP in the aqueous humour (14.8 +/- 0.8 nmol 1(-1)) and to induce symptoms of ocular inflammation. The elevation in concentration of CGRP induced by sodium nitroprusside was not affected by L-NAME (200 mg kg(-1)) (14.5 +/- 1.2 nmol 1(-1)). Ocular responses were not inhibited by L-NAME. 6 Our findings suggest that NO plays an important role in ocular inflammation by activating C-fibres (directly or indirectly) and by mediating CGRP-induced responses.