title: Role of nitric oxide (NO) in ocular inflammation.
abstract: 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, NG-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 l-1. Irradiation of the iris raised the CGRP concentration to 8.9 +/- 1.5 nmol l-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 l-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 l-1. 5. In addition, a NO donor, sodium nitroprusside (0.9 mumol), was found to raise the concentration of CGRP in the aqueous humour (14.8 +/- 0.8 nmol l-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 l-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.
authors.affiliation: Department of Pharmacology, University of Lund, Sweden.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Håkanson
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001082:Aqueous Humor / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005128:Eye Diseases / Q000188:drug therapy / Q000503:physiopathology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007259:Infrared Rays; D007498:Iris / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019331:NG-Nitroarginine Methyl Ester; D009412:Nerve Fibers / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester