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, 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.
Wang
Z Y
ZY
Department of Pharmacology, University of Lund, Sweden.
Håkanson
R
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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
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