Incubation of porcine iris-ciliary bodies to study the mechanisms by which nitric oxide donors lower intraocular pressure.
BACKGROUND
We previously reported that several nitric oxide (NO) donors, guanylate cyclase activators, and cyclic GMP lower intraocular pressure (IOP) in rabbits.


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.
Kotikoski
Hanna
H
Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, University of Helsinki, Finland.
Kankuri
Esko
E
Vapaatalo
Heikki
H
D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002924:Ciliary Body / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D007429:Intraocular Pressure / Q000502:physiology*; D007498:Iris / Q000378:metabolism*; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology; D009589:Nitrogen Oxides; D010069:Oxadiazoles / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D026403:S-Nitrosothiols / Q000494:pharmacology; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013552:Swine; D013997:Time Factors
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D009574:Nitro Compounds; D009589:Nitrogen Oxides; D010069:Oxadiazoles; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D011810:Quinoxalines; D026403:S-Nitrosothiols; C110881:S-nitro-N-acetylpenicillamine; C060039:S-nitrosocaptopril; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; C061872:FK 409; D002216:Captopril; D006162:Guanylate Cyclase; D010396:Penicillamine; C011145:zaprinast; D006152:Cyclic GMP