OCULAR INFLAMMATION-INDUCED BY ELECTROCONVULSIVE TREATMENT - CONTRIBUTION OF NITRIC-OXIDE AND NEUROPEPTIDES MOBILIZED FROM C-FIBERS

1 Electroconvulsive treatment (ECT) of rabbits produced ocular inflamm ation consisting of conjunctival hyperaemia, miosis and protein extrav asation into the aqueous humour, reflected by the so-called aqueous fl are response (AFR); the maximal reduction in pupil size was 3.8 +/- 0. 1 mm (s.e. of mean, n = 16) while the maximal AFR was 28.1 +/- 2.8 (ar bitrary units). 2 ECT also caused release of substance P (SP), pituita ry adenylate cyclase-activating peptide (PACAP)-27, -38 and calcitonin gene-related peptide (CGRP). The concentrations of SP and CGRP in the aqueous humour of normal, untreated eyes were 10.6 +/- 1.4 and 117.4 +/- 12.4 pmol l(-1), respectively, while the concentrations of PACAP-2 7 and -38 were below the detection limit. After ECT the concentrations of SP, PACAP-27, -38 and CGRP were 65.0 +/- 9.6, 46.9 +/- 8.4, 50.2 /- 5.4 and 1109.9 +/- 133.1 pmol l(-1), respectively (s.e. of mean, n = 12). Conceivably, ECT evoked an antidromic activation of sensory neu rones in the trigeminal ganglion with the consequent release of neurop eptides from C-fibres in the uvea and the development of neurogenic in flammation. 3 Rabbits received the nitric oxide (NO) synthase inhibito r, N-G-nitro-L-arginine methyl ester (L-NAME, 200 mg kg(-1), i.v.). Th is pretreatment inhibited the ECT evoked conjunctival hyperaemia, mios is and AFR; under these circumstances the maximal reduction in pupil s ize was 1.9 +/- 0.1 mm while the maximal AFR was 2.7 +/- 0.9 (n = 16). L-NAME also inhibited the ECT-evoked release of SP, PACAP-27, -38 and CGRP into the aqueous humour; the concentrations of SP and CGRP were 13.2 +/- 1.5 and 204.8 +/- 33.5 pmol l(-1), respectively, while PACAP- 27 and -38 were below the detection limit (n = 12). 4 The ECT-evoked m iosis was also inhibited by pretreatment with the tachykinin receptor antagonist D-Pal(9) spantide II (90 nmol, intravitreal injection); und er these circumstances the maximal reduction in pupil size was only 0. 7 +/- 0.03 mm, indicating an important role for SP in the miotic respo nse. Pretreatment of the eye with capsaicin, which is known to cause f unctional ablation of C-fibres, inhibited the conjunctival hyperaemia, miosis and AFR by 40-50%; the maximal reduction in pupil size being 2 .2 +/- 0.2 mm and the maximal AFR 13.8 +/- 2.1 (arbitrary units) (n = 8). 5 The results suggest (1) that ECT evokes ocular inflammation thro ugh antidromic C-fibre activation; (2) that SP contributes to the ECT- evoked miosis; and (3) that NO contributes to the antidromic C-fibre a ctivation and possibly to the vascular responses mediated by the C-fib re transmitters.