Zy. Wang et al., THE CONTRIBUTION OF NITRIC-OXIDE TO ENDOTOXIN-INDUCED OCULAR INFLAMMATION - INTERACTION WITH SENSORY NERVE-FIBERS, British Journal of Pharmacology, 118(6), 1996, pp. 1537-1543
1 The actions of nitric oxide (NO) have been investigated in an endoto
xin-evoked ocular inflammatory model in the rabbit, with particular em
phasis on the relationship between NO, sensory nerves (C-fibres) and t
he C-fibre neuropeptides, calcitonin gene-related peptide (CGRP) and p
ituitary adenylate cyclase activating peptide (PACAP). 2 Endotoxin, in
jected intravitreally, evoked inflammatory responses, i.e. conjunctiva
l hyperaemia, miosis and protein extravasation, reflected by the aqueo
us flare response (AFR). In control rabbits, the maximum AFR was 66.59.5 (arbitrary units). Pretreatment with the NO synthase (NOS) inhibit
or, NG-nitro-L-arginine (L-NAME, 200 mg kg(-1)) given by intravenous i
njection, inhibited the endotoxin-evoked responses; the AFR was 16.5+/
-1.9 (n=8, P<0.001) and the conjunctival hyperaemia was abolished. 3 E
ndotoxin-evoked ocular inflammation is associated with the release of
CGRP and PACAP from C-fibres. In the eyes challenged with endotoxin, t
he concentrations of PACAP-27, -38 and CGRP in the aqueous humour were
58.2+/-10.9, 54.4+/-12.4 and 5526+/-519 (pmol l(-1)), respectively. L
-NAME inhibited the release of PACAP-27, -38 and CGRP; the concentrati
ons were 14.3+/-2.5, 13.5+/-2.5 and 510+/-67 (pmol l(-1)), respectivel
y (n=8, P<0.01 or 0.001). 4 Intravitreal injection of 0.3 nmol CGRP in
duced conjunctival hyperaemia and AFR; the maximum AFR was 140.2+/-11.
4. L-NAME suppressed the response induced by CGRP; the AFR was 23.4+/-
5.5 (n=8, P<0.001). L-NAME abolished the conjunctival hyperaemia induc
ed by PACAP-27 and -38 (0.3 nmol) and seduced the AFR. 5 The inflammat
ory cells that infiltrated the uvea, cornea and aqueous humour in larg
e numbers in response to intravitreal injection of endotoxin were foun
d to express inducible NOS. L-NAME prevented the appearance of such ce
lls. 6 Our findings suggest that NO plays an important role in the end
otoxin-evoked ocular inflammation in the rabbit: NO activates C-fibres
causing release of C-fibre neuropeptides into the aqueous humour. In
addition, NO mediates some of the ocular effects of CGRP and PACAP, si
nce L-NAME suppressed the AFR induced by these peptides.