Nitric oxide/guanylate cyclase pathways and flow in anterior segment perfusion.
BACKGROUND
The nitric oxide/guanylate cyclase pathway has been suggested to participate in the regulation of intraocular pressure. In the present study, the involvement of nitric oxide pathways on the outflow through the trabecular meshwork was assessed using pharmacological manipulation of the nitric oxide pathway.


METHODS
Anterior segments of human donor eyes were maintained in an organ culture perfusion system, and the effects of L-NAME, an inhibitor of nitric oxide synthase, on the flow rate was determined. In a second series, the effects of consecutive application of L-arginine as substrate for nitric oxide synthase, L-NAME, and sodium nitroprusside, a nitric oxide-donor, were studied. The cyclic GMP levels in the perfusate were assessed with an ELISA immunoassay kit.


RESULTS
In the first series of experiments, L-NAME caused a statistically significant decrease in flow rate of 10%, accompanied by a decrease in cGMP levels. In the second series, L-arginine did not alter flow, and the effect of L-NAME seen in the first series was prevented by the high preload of L-arginine. Nitroprusside caused a significant 10% increase of flow rate. In the perfusate, cGMP levels were not altered by L-arginine and L-NAME, but were increased after nitroprusside.


CONCLUSIONS
Under organ culture perfusion conditions, modulation of the nitric oxide/guanylate cyclase system alters the flow rate through the trabecular meshwork within a total range of 20%; i.e. the difference between inhibition of NO synthesis and the presence of a NO-donor. These results indicate that the nitric oxide/guanylate cyclase system plays a role in aqueous humour dynamics and, therefore, in the regulation of intraocular pressure.
Schneemann
Andrea
A
Glaucoma Research Group, The Netherlands Ophthalmic Research Institute, KNAW, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
Dijkstra
Berlinde G
BG
van den Berg
Thomas J
TJ
Kamphuis
Willem
W
Hoyng
Philip F J
PF
D000328:Adult; D000368:Aged; D000869:Anterior Eye Segment / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009924:Organ Culture Techniques; D010477:Perfusion; D014129:Trabecular Meshwork / Q000502:physiology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester