We conclude that enhancement of outflow facility by nitrosocaptopril, SNP and 8-Br-cGMP, their second messenger derivative, at least partly explains the IOP-lowering effect of NO releasing compounds.

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.

ABSTRACT.Purpose: To study the role of the L-arginine-nitric oxide (NO) pathway in aqueous humour dynamics by measuring nitrate, nitrite and cyclic (cGMP) levels in guanosine 3ƒ,5ƒ-monophosphate the aqueous humour of glaucomatous and nonglaucomatous cataract patients. Methods: The study involved 38 glaucoma patients undergoing unilateral cataract surgery in the glaucomatous eye and 38 cataract control patients matched for sex, age, smoking habits and organic nitrate medication. All subjects underwent ophthalmic examination, and blood pressure was measured preoperatively. Nitrite, nitrate and cGMP levels were measured in aqueous humour and serum. Results: The NO x (nitrite π nitrate), nitrite and cGMP concentrations in the aqueous humour were slightly higher in the glaucoma patients than in the control patients, but the differences did not reach statistical significance. The levels of cGMP in serum were higher in the glaucoma patients (P Ω 0.053). The subgroup of glaucoma patients with pseudoexfoliation had lower NO x and nitrite values in the aqueous humour (P Ω 0.046 and P Ω 0.345, respectively) than the matched controls, while cGMP levels were higher (P Ω 0.043). Levels of NO x and nitrite in the aqueous humour were higher in patients using oral nitroglycerin (P Ω 0.062 and P Ω 0.042, respectively) than in patients without this medication. Blood pressure was higher in the glaucoma patients, with a mean of 165/89 mmHg as compared to 153/81 mmHg in the controls (P-values 0.071/0.008). Conclusions: No differences in NO metabolites were found between glaucoma and control patients. However, any real changes may have been disguised by optimal medication of glaucoma. Low NO x and high cGMP levels in the aqueous humour of pseudoexfoliation patients warrant further evaluation in a larger study.

Novel 1-R-imidazole-2-nitrolic acids and 1-R-imidazole-5-nitrolic acids (R: H, Me, Bn) were synthesized from oximes by treatment with a mixture of fuming nitric acid and acetic acid. The effects of these potential nitric oxide-donating compounds were tested on ocular variables such as intraocular pressure and formation of cyclic guanosine-3,5'-monophosphate in the incubation of porcine iris-ciliary body.