Involvement of hydrogen sulfide in perivascular and hypoxia-induced inhibition of endothelin contraction in porcine retinal arterioles

Winther, Anna K.; Dalsgaard, Tage; Hedegaard, Elise Røge; Simonsen, Ulf

doi:10.1016/j.niox.2015.07.002

Cited by 7 publications

(9 citation statements)

References 47 publications

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“…In bovine retinal arteries, Takir et al 78 found that relaxations of PGF 2a -and potassium-induced tone elicited by NaHS were blocked by inhibitors of voltage-dependent potassium channels and inwardly rectifying potassium channels suggesting that H 2 S could play a major role in the regulation of retinal arterial tone through an action on these channels. In endothelin precontracted porcine retinal arterioles, Winther et al 79 demonstrated that both GYY4137 and NaHS evoked concentration-dependent relaxations that were consistent with reports from other investigators. 75,78 Interestingly, inhibitors of H 2 S biosynthetic enzymes, aminooxyacetic acid and propargylglycine, enhanced the endothelin contractions, a response that was more pronounced in hypoxic (1% O 2 ) conditions.…”

Section: Ocular Vasculaturesupporting

confidence: 76%

Regulation of Aqueous Humor Dynamics by Hydrogen Sulfide: Potential Role in Glaucoma Pharmacotherapy

Ohia

Robinson

Mitchell

et al. 2018

Journal of Ocular Pharmacology and Therapeutics

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Hydrogen sulfide (HS) is a gaseous transmitter with well-known biological actions in a wide variety of tissues and organs. The potential involvement of this gas in physiological and pathological processes in the eye has led to several in vitro, ex vivo, and in vivo studies to understand its pharmacological role in some mammalian species. Evidence from literature demonstrates that 4 enzymes responsible for the biosynthesis of this gas (cystathionine β-synthase, CBS; cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3MST; and d-amino acid oxidase) are present in the cornea, iris, ciliary body, lens, and retina. Studies of the pharmacological actions of HS (using several compounds as fast- and slow-releasing gas donors) on anterior uveal tissues reveal an effect on sympathetic neurotransmission and the ability of the gas to relax precontracted iris and ocular vascular smooth muscles, responses that were blocked by inhibitors of CSE, CBS, and K channels. In the retina, there is evidence that HS can inhibit excitatory amino acid neurotransmission and can also protect this tissue from a wide variety of insults. Furthermore, exogenous application of HS-releasing compounds was reported to increase aqueous humor outflow facility in an ex vivo model of the porcine ocular anterior segment and lowered intraocular pressure (IOP) in both normotensive and glaucomatous rabbits. Taken together, the finding that HS-releasing compounds can lower IOP and can serve a neuroprotective role in the retina suggests that HS prodrugs could be used as tools or therapeutic agents in diseases such as glaucoma.

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Section: Ocular Vasculaturesupporting

confidence: 76%

Regulation of Aqueous Humor Dynamics by Hydrogen Sulfide: Potential Role in Glaucoma Pharmacotherapy

Ohia

Robinson

Mitchell

et al. 2018

Journal of Ocular Pharmacology and Therapeutics

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“… 22 , 23 The role of H 2 S in retinal pathophysiological changes has been appreciated in the past decade. Studies discovered several protective properties of H 2 S in a variety of conditions, including protecting retina from light-induced degeneration by suppression of Ca 2+ influx, 10 attenuating excitotoxic neurotransmission, 9 protecting retinal neuronal cell apoptosis against NMDA or retinal ischemia-reperfusion–induced injury via its antioxidative activity, 11 , 12 , 24 inducing retinal vascular relaxation, 25 , 26 and alleviating retinal oxidative stress and inflammation in a rat model of streptozotocin-induced diabetes. 27 In spite of this progress, the function of H 2 S in neovascular disease in the retina is unknown, although increased plasma and vitreous H 2 S has been found in patients with proliferative diabetic retinopathy, 28 and H 2 S exhibits proangiogenic property in organs where ischemic vessel growth is beneficial.…”

mentioning

confidence: 99%

Hydrogen Sulfide Contributes to Retinal Neovascularization in Ischemia-Induced Retinopathy

Gersztenkorn

Coletta

Zhu

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeHydrogen sulfide (H2S) is an endogenous gaseous signaling molecule with significant pathophysiological importance, but its role in retinal neovascular diseases is unknown. Hydrogen sulfide is generated from L-cysteine by cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and/or 3-mercaptopyruvate sulfurtransferase (3-MST). The aim of this study was to investigate the role of H2S in retinal neovascularization (NV) in ischemia-induced retinopathy.MethodsStudies were performed in a murine model of oxygen-induced retinopathy (OIR). Hydrogen sulfide was detected with a fluorescent assay. Western blots and immunohistochemistry were used to assess the changes of H2S-producing enzymes. Gene deletion and pharmacologic inhibition were used to investigate the role of H2S in retinal NV.ResultsHydrogen sulfide production was markedly increased in retinas from OIR mice compared with those from room air (RA) controls. Cystathionine-β-synthase and CSE were significantly increased in OIR retinas, whereas 3-MST was not changed. Cystathionine-β-synthase was expressed throughout the neuronal retina and upregulated in neurons and glia during OIR. Cystathionine-γ-lyase was also localized to multiple retinal layers. Its immunoreactivity was prominently increased in neovascular tufts in OIR. Pharmacologic inhibition of CBS/CSE or genetic deletion of CSE significantly reduced retinal NV in OIR.ConclusionsOur data indicate that the H2S-generating enzymes/H2S contributes to retinal NV in ischemia-induced retinopathy and suggest that blocking this pathway may provide novel therapeutic approaches for the treatment of proliferative retinopathy.

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“…32 The H 2 S donor GYY4137 is able to induce a substantial vasorelaxation in porcine retinal arterioles and the H 2 S donor NaHS in porcine and bovine retinal arteries. 18,33 The NaHS-induced relaxation is reduced in the presence of 100 mM K þ , just like the RRFinduced relaxation. Further research revealed that the H 2 S relaxation was endothelium, NO, COX, guanylyl cyclase, and adenylyl cyclase independent, but that K ir and K V channels are involved.…”

Section: Retinal Relaxing Factor and Hydrogen Sulfidementioning

confidence: 96%

“…2,17 Winther et al found that the hypoxia-induced vasorelaxation was present in porcine retinal arterioles with and without adhering retinal tissue. 18 Delaey et al provided evidence that the hypoxic vasodilation on bovine retinal arteries is largely regulated by an indirect effect from the retina. The induction of acute hypoxia in bovine retinal arteries without surrounding retinal tissue resulted in only a small relaxation, but when hypoxia was induced in the arteries with surrounding retinal tissue, it resulted in a large relaxation.…”

Section: Retinal Relaxing Factor In Hypoxia-induced Relaxationmentioning

confidence: 99%

“…10 This finding was confirmed on pigs, mice, and rats. 6,7,18,19 Furthermore, it was discovered that direct contact between the retina and the blood vessel was not necessary for the hypoxic vasorelaxation, indicating the involvement of a diffusible factor. 10 The potential involvement of different hypoxia-induced vasorelaxants was tested.…”

Section: Retinal Relaxing Factor In Hypoxia-induced Relaxationmentioning

confidence: 99%

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The Retinal Relaxing Factor: Update on an Enigmatic Regulator of the Retinal Circulation

Daele

Boydens

Pauwels

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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The retinal circulation is regulated by different local factors and might include the retinal relaxing factor (RRF). This factor is found to be continuously released by the retina and relaxes smooth muscle cells. This review describes the current knowledge about the RRF. Despite many research efforts, the cellular source, identity, mechanism, and physiological role of the RRF remain largely unknown. Thus far, it seems that the RRF is a hydrophilic, thermostable, diffusible chemical messenger, which characteristics do not correspond with most well-known endogenous vasorelaxants. The RRF-induced relaxation seems to rely on activation of the inward rectifier K+ channels and the Rho kinase Ca2+ sensitization mechanism. Voltage-dependent K+ channels and plasma membrane Ca2+-ATPase might also be involved, whereas the involvement of cyclooxygenase is still a point of discussion. Furthermore, it appears that the RRF is involved in other relaxation pathways, namely those of hypoxia, adenosine, and adenosine triphosphate, hydrogen sulfide, γ-aminobutyric acid, and dorzolamide.

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Involvement of hydrogen sulfide in perivascular and hypoxia-induced inhibition of endothelin contraction in porcine retinal arterioles

Cited by 7 publications

References 47 publications

Regulation of Aqueous Humor Dynamics by Hydrogen Sulfide: Potential Role in Glaucoma Pharmacotherapy

Regulation of Aqueous Humor Dynamics by Hydrogen Sulfide: Potential Role in Glaucoma Pharmacotherapy

Hydrogen Sulfide Contributes to Retinal Neovascularization in Ischemia-Induced Retinopathy

The Retinal Relaxing Factor: Update on an Enigmatic Regulator of the Retinal Circulation

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