THE CONTRIBUTION OF NITRIC-OXIDE TO ENDOTOXIN-INDUCED OCULAR INFLAMMATION - INTERACTION WITH SENSORY NERVE-FIBERS

Citation
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
Citations number
21
Categorie Soggetti
Pharmacology & Pharmacy",Biology
ISSN journal
00071188
Volume
118
Issue
6
Year of publication
1996
Pages
1537 - 1543
Database
ISI
SICI code
0007-1188(1996)118:6<1537:TCONTE>2.0.ZU;2-K
Abstract
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.