title: Comparison of nitric oxide donors in lowering intraocular pressure in rabbits: role of cyclic GMP.
abstract: L-arginine-nitric oxide (NO) pathway participates in the physiology and in many pathological processes in the eye, such as glaucoma. The aim of the present study was to compare the ocular hypotensive effect of different NO-donors, and to get 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 (microM, decrease in IOP 50%), atriopeptin II (84 (microM 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 (microM, 25%), zaprinast + SNP (1 mM + 40 mM, 22%), spermine NONOate (100 mM, 20%) [corrected]. The decrease in IOP lasted for 2-5 hr, except with atriopeptin II and III, when IOP values were first normalized in 6 hr and 2 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.
authors.affiliation: Institute of Biomedicine, Biomedicum Helsinki, Pharmacology, University of Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Kotikoski
authors.forename: Päivi
authors.initials: P
authors.lastname: Alajuuma
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.forename: Pertteli
authors.initials: P
authors.lastname: Salmenperä
authors.forename: Olli
authors.initials: O
authors.lastname: Oksala
authors.forename: Pekka
authors.initials: P
authors.lastname: Laippala
authors.forename: Heikki
authors.initials: H
authors.lastname: Vapaatalo
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D005260:Female; D007191:Indazoles / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011688:Purinones / Q000494:pharmacology; D011817:Rabbits
chemical_list: D007191:Indazoles; D020030:Nitric Oxide Donors; D011688:Purinones; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D001120:Arginine; D019001:Nitric Oxide Synthase; C011145:zaprinast; D006152:Cyclic GMP