Nitric oxide and cyclic GMP enhance aqueous humor outflow facility in rabbits

Kotikoski, Hanna; Vapaatalo, Heikki; Oksala, Olli

doi:10.1076/ceyr.26.2.119.14511

Cited by 72 publications

(51 citation statements)

References 9 publications

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“…In contrast, it is inconsistent with results by Kosior-Jarecka et al [24] , who reported that there was no significant difference in aqueous humor levels of NO between 14 patients with POAG, 12 patients with CCAG and control subjects (p = 0.535). However, the increased level of total nitrite in aqueous humor in the present study could be explained as an attempt of the eye to increase the aqueous humor outflow facility through the IOP-lowering effect of NO/cyclic guanosine monophosphate [25] . In the current study, there was no correlation between aqueous humor and plasma levels of ET-1 and NO; results suggested that levels of ET-1 and NO in aqueous humor were not related to breakdown of blood-retinal barrier and/or ocular blood.…”

Section: Discussionmentioning

confidence: 59%

Endothelin-1 and Nitric Oxide Levels in Patients with Glaucoma

2011

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Aims: To investigate the levels of endothelin-1 (ET-1) and nitric oxide (NO) in the aqueous humor and plasma of human eyes with different types of glaucoma: primary open-angle glaucoma (POAG) and chronic closed-angle glaucoma (CCAG). Methods: Patients were classified into 3 groups: group I comprised 35 patients with POAG, group II comprised 25 patients with CCAG, and 30 patients with senile cataract (group III) were used as a control group. Aqueous humor and corresponding plasma were analyzed for ET-1 and NO concentrations by enzyme-linked immunosorbent assay. A Bonferroni correction for multiple comparisons was performed. Results: There was no significant difference in plasma levels of either ET-1 or NO metabolites between the groups studied. ET-1 and NO were significantly elevated in the aqueous humor of patients with CCAG and POAG compared to the corresponding value in patients with cataract (p < 0.001). ET-1 and NO concentrations in the aqueous humor were more marked in CCAG than in POAG. NO levels were correlated with ET-1 in the aqueous humor of patients with glaucoma (p < 0.001). Conclusions: Increased concentrations of ET-1 and NO in aqueous humor may be useful with POAG and CCAG. In addition, ET-1 and NO may have useful metabolite levels in the aqueous humor of POAG and CCAG patients as a result of glaucoma damage and may not be a cause of it.

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Section: Discussionmentioning

confidence: 59%

Endothelin-1 and Nitric Oxide Levels in Patients with Glaucoma

2011

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“…Some studies have shown that both topical and intraocular administration of NO donors reduced IOP [30][31][32], while others reported that topical NO donors increased the IOP without affecting aqueous humor formation [33] or outfl ow facility [34] . Yet, other studies have shown that NO donors have no effect on the IOP in rabbits [35] or humans [36] .…”

Section: Discussionmentioning

confidence: 99%

Morphine-Induced Reduction of Intraocular Pressure and Pupil Diameter: Role of Nitric Oxide

Dortch-Carnes

Russell²

2006

Pharmacology

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The present study was performed to evaluate the role of nitric oxide in the intraocular pressure (IOP) lowering effect and in the miotic action of morphine. The IOP was measured in conscious, normal, dark-adapted New Zealand white rabbits using a calibrated pneumatonometer. Experiments were conducted, in which rabbits’ eyes were treated with morphine topically and unilaterally, while the fellow eyes received vehicle. IOP and pupil diameter (PD) measurements were taken 0.5 and 0 h before morphine administration and 0.5, 1, 2, 3, 4, and 5 h thereafter. The effects of a nonselective opioid receptor antagonist (naloxone), a nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester; L-NAME), and a sulfhydryl reagent (reduced L-glutathione; GSH) on morphine-mediated changes in IOP and PD were also determined. Morphine (10, 33, and 100 µg) produced concen- tration-dependent decreases in IOP and reduced PD in both treated and untreated eyes of New Zealand white rabbits. IOP-lowering effect of morphine (100 µg) and reduction in PD were both significantly inhibited by pretreatment with naloxone (100 µg), L-NAME (0.5%), or GSH (100 µg). The results from this study indicate that morphine-induced ocular hypotension and reduction in PD are opioid-receptor-mediated responses that are associated with the release of nitric oxide. Because the µ3 opioid receptor subtype has a nitric-oxide-releasing activity and is sensitive to inactivation by GSH, it is concluded that morphine-induced ocular hypotension and miosis are mediated, in part, by activation of µ3 opioid receptors.

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“…Topical application of NO donors to rabbit eyes [35] reduced IOP by increasing the rate of aqueous humor outflow through the conventional outflow pathway [36]. Studies have also shown that intravitreal and intracameral injections of NO donors in rabbits caused a drastic decrease in IOP, which was correlated with nitrite production indicating that NO was released [37].…”

Section: Nitric Oxide Regulation Of Iopmentioning

confidence: 99%

“…sGC has binding sites for gases such as NO and carbon dioxide and other ligands that are NO-independent, such as YC1. Activators of both mGC and sGC have been shown to decrease IOP in humans, rabbit and monkey [35][36][37][38][55][56][57][58][59][60][61][62][63] thus providing a physiological role for the guanylate cyclases in IOP regulation. Because the natriuretic peptides cannot be absorbed in the eye, our study focuses on activators of sGC.…”

Section: Guanylate Cyclase and Iopmentioning

confidence: 99%

Guanylate Cyclase Activators, Cell Volume Changes and IOP Reduction

Ellis¹

2011

Cell Physiol Biochem

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Glaucoma afflicts millions of people worldwide and is a major cause of blindness. The risk to develop glaucoma is enhanced by increases in IOP, which result from deranged flow of aqueous humor. Aqueous humor is a fluid located in the front of the eye that gives the eye its buoyancy and supplies nutrients to other eye tissues. Aqueous humor is secreted by a tissue called ciliary processes and exits the eye via two tissues; the trabecular meshwork (TM) and Schlemm’s canal. Because the spaces through which the fluid flows get smaller as the TM joins the area of the Schlemm’s canal, there is resistance to aqueous humor outflow and this resistance creates IOP. There is a correlation between changes in TM and Schlemm’s canal cell volume and rates of aqueous humor outflow; agents that decrease TM and Schlemm’s canal cell volume, increase the rate of aqueous humor outflow, thus decreasing IOP. IOP is regulated by guanylate cyclase activators as shown in humans, rabbits and monkeys. There are two distinct groups of guanylate cyclases, membrane guanylate cyclase and soluble guanylate cyclase (sGC); activation of both have been shown to decrease IOP. Members of the membrane guanylate cyclase family of receptors bind to peptide ligands, while the sGC responds to gases (such as NO and CO₂) and compounds (such as YC1, [3-(5’-hydroxymethyl-2’furyl)-1-benzyl indazole), a benzyl indazole derivative, and BAY-58-2667); activation of either results in formation of cyclic GMP (cGMP) and activation of protein kinase G (PKG) and subsequent phosphorylation of target proteins, including the high conductance calcium activated potassium channel (BKca channel). While activators of both membrane guanylate cyclase and sGC have the ability to lower IOP, the IOP lowering effects of sGC are noteworthy because sGC activators can be topically applied to the eye to achieve an effect. We have demonstrated that activators of sGC increase the rate at which aqueous humor exits the eye in a time course that correlates with the time course for sGC-induced decreases in TM and Schlemm’s canal cell volume. Additionally, sGC-induced decrease in cell volume is accompanied by both K⁺ and Cl^- efflux induced by activation of K⁺ and Cl^- channels, including the BKca channel and/or K⁺Cl^- symport. This suggests that parallel K⁺Cl^- efflux, and resultant H₂O efflux result in decreases in cell volume. These observations suggest a functional role for sGC activators, and suggest that the sGC/cGMP/PKG systems are potential therapeutic targets in the treatment of glaucoma.

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Nitric oxide and cyclic GMP enhance aqueous humor outflow facility in rabbits

Abstract: 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.

Cited by 72 publications

References 9 publications

Endothelin-1 and Nitric Oxide Levels in Patients with Glaucoma

Endothelin-1 and Nitric Oxide Levels in Patients with Glaucoma

Morphine-Induced Reduction of Intraocular Pressure and Pupil Diameter: Role of Nitric Oxide

Guanylate Cyclase Activators, Cell Volume Changes and IOP Reduction

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