ArticleCirculation research2008
Nitroglycerin-induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance.
Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 118 citations in OpenAlex.
- S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia.British journal of clinical pharmacology · 2014Trial
- NO-cGMP Signaling in Endothelial Function of the Healthy and Inflamed Dental Pulp.International journal of molecular sciences · 2025Review
- Soluble guanylyl cyclase, the NO receptor, drives vasorelaxation via endothelial S-nitrosation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- S-Nitrosylation in Cardiovascular Disorders: The State of the Art.Biomolecules · 2025Review
- Challenging the Norm: The Unrecognized Impact of Soluble Guanylyl Cyclase Subunits in Cancer.International journal of molecular sciences · 2024Review
- Inhibitory Peptide of Soluble Guanylyl Cyclase/Trx1 Interface Blunts the Dual Redox Signaling Functions of the Complex.Antioxidants (Basel, Switzerland) · 2023Article
- Cellular Factors That Shape the Activity or Function of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase.Cells · 2023Review
- Nitric oxide augments signaling for contraction in hypoxic pulmonary arterial smooth muscle-Implications for hypoxic pulmonary hypertension.Frontiers in physiology · 2023Article
- Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease.International journal of molecular sciences · 2022Review
- Soluble guanylyl cyclase: Molecular basis for ligand selectivity and actionFrontiers in molecular biosciences · 2022Review
- Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance.Molecules (Basel, Switzerland) · 2021Review
- Higher susceptibility to heme oxidation and lower protein stability of the rare αBiochemical pharmacology · 2021Article
- S-Nitrosylation of Akt by organic nitrate delays revascularization and the recovery of cardiac function in mice following myocardial infarction.Journal of cellular and molecular medicine · 2021Article
- Selective cysteines oxidation in soluble guanylyl cyclase catalytic domain is involved in NO activation.Free radical biology & medicine · 2021Article
- Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease.Scientific reports · 2020Article
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- S-nitrosylation of endothelial nitric oxide synthase impacts erectile function.International journal of impotence research · 2019Article
- S-nitrosylation of NOS pathway mediators in the penis contributes to cavernous nerve injury-induced erectile dysfunction.International journal of impotence research · 2018Article
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- Guanylyl cyclase sensitivity to nitric oxide is protected by a thiol oxidation-driven interaction with thioredoxin-1.The Journal of biological chemistry · 2017Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Nitrates such as nitroglycerin (GTN) and nitric oxide donors such as S-nitrosothiols are clinically vasoactive through stimulation of soluble guanylyl cyclase (sGC), which produces the second messenger cGMP. Development of nitrate tolerance, after exposure to GTN for several hours, is a major drawback to a widely used cardiovascular therapy. We recently showed that exposure to nitric oxide and to S-nitrosothiols causes S-nitrosylation of sGC, which directly desensitizes sGC to stimulation by nitric oxide. We tested the hypothesis that desensitization of sGC by S-nitrosylation is a mechanism of nitrate tolerance. Our results established that vascular tolerance to nitrates can be recapitulated in vivo by S-nitrosylation through exposure to cell membrane-permeable S-nitrosothiols and that sGC is S-nitrosylated and desensitized in the tolerant, treated tissues. We next determined that (1) GTN treatment of primary aortic smooth muscle cells induces S-nitrosylation of sGC and its desensitization as a function of GTN concentration; (2) S-nitrosylation and desensitization are prevented by treatment with N-acetyl-cysteine, a precursor of glutathione, used clinically to prevent development of nitrate tolerance; and (3) S-nitrosylation and desensitization are reversed by cessation of GTN treatment. Finally, we demonstrated that in vivo development of nitrate tolerance and crosstolerance by 3-day chronic GTN treatment correlates with S-nitrosylation and desensitization of sGC in tolerant tissues. These results suggest that in vivo nitrate tolerance is mediated, in part, by desensitization of sGC through GTN-dependent S-nitrosylation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.