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Incubation of porcine iris-ciliary bodies to study the mechanisms by which nitric oxide donors lower intraocular pressure.

Abstract：

BACKGROUND:We previously reported that several nitric oxide (NO) donors, guanylate cyclase activators, and cyclic GMP lower intraocular pressure (IOP) in rabbits. MATERIAL/METHODS:This study evaluated a novel method for studying cGMP production in the iris-ciliary body after the administration of different NO donors and guanylate cyclase activators. Tissue samples of porcine iris-ciliary body were incubated for 30 or 60 minutes with the test compounds and with or without the phosphodiesterase inhibitor zaprinast. The concentration of cGMP in the iris-ciliary body as an indicator of soluble guanylate cyclase activation was measured by radioimmunoassay. RESULTS:The tested NO donors - SNOG, NONOate, NOR-3, and SNAP - were shown to release NO in incubation medium, and clearly increase cGMP concentration in the iris-ciliary body. Cyclic GMP production was 2-5 times higher with nitrosocaptopril and about 10 times higher with SNP than in the unstimulated control tissue incubation. Captopril, the reference for nitrosocaptopril, did not induce cGMP production in the porcine iris-ciliary body. ODQ, a guanylate cyclase inhibitor, shut down the production of cGMP after the administration of nitrosocaptopril and SNP. The guanylate cyclase activators YC-1 and atriopeptin III increased cGMP dose-dependently. CONCLUSIONS:In this novel tissue incubation method, several NO donors and guanylate cyclase activators increased cGMP production in the porcine iris-ciliary body. This method can be used to screen new molecules in terms of cGMP production, since the ciliary body is important in lowering intraocular pressure.

journal_name

Med Sci Monit

journal_title

Medical science monitor : international medical journal of experimental and clinical research

authors

Kotikoski H,Kankuri E,Vapaatalo H

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

BR1-7

issue

1

eissn

1234-1010

issn

1643-3750

pii

3232

journal_volume

9

pub_type

杂志文章

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