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Abstract #6860 Published in IGR 4-1
Comparison of nitric oxide donors in lowering intraocular pressure in rabbits: Role of cyclic GMP
Kotikoski H; Alajuuma P; Moilanen E; Salmenpera P; Oksala O; Laippala P; Vapaatalo HJournal of Ocular Pharmacology and Therapeutics 2002; 18: 11-23
L-arginine-nitric oxide (NO) pathway participates in the physiology of, and in many pathological processes of, the eye, such as glaucoma. The aim of the present study was to compare the ocular hypotensive effect of different NO-donors, and to obtain more information on the role of cyclic guanosine 3',5'-monophosphate (cGMP) in this process. The test compounds were administered topically or intravitreally in the eye of a normotensive rabbit. Intraocular pressure (IOP) was measured with a pneumatonometer after topical anesthesia. The metabolites of NO (nitrite, nitrate, NOx) and cGMP were assayed from the aqueous humor and plasma. NO-synthase (NOS) protein expression was assayed in the ciliary body by Western blotting. The maximal lowering of IOP was achieved as follows: atriopeptin III (concentration 78 (M, decrease in IOP 50%), atriopeptin II (84 (M, 37%), 8-Br-cGMP (90 mM, 37%), zaprinast + 8-Br-cGMP (1 mM + 90 mM, 34%), L-arginine (1 mM, 29%), SNP (40 mM, 28%), nitrosocaptopril (100 mM, 28%), S-nitrosothiol (SNOG) (10 mM, 27%), YC-1 (10 (M, 25%), zaprinast + SNP (1 mM + 40 mM, 22%), spermine NONOate (100 mM, 20%). The decrease in IOP lasted for two ti five hours, except with atriopeptin II and III, when IOP values were first normalized in six hours and two days, respectively. In conclusion, the results of the present study indicate that by increasing the activity of L-arginine/NO/cGMP-pathway it is possible to lower IOP in rabbits equally to the currently used antiglaucomatous drugs.
Dr. H. Vapaatalo, Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, P.O. Box 63, FIN-00014 Helsinki, Finland. heikki.vapaatalo@helsinki.fi
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
