Cited by 2,310Sulfur Compounds in BiologyNitric Oxide and Endothelin EffectsHeme Oxygenase-1 and Carbon Monoxide

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H 2 S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine γ-Lyase

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Yang, Guangdong, Wu, Lingyun, Jiang, Bo, Yang, Wei, Qi, Jiansong, Cao, Kun, Meng, Qinghe, Mustafa, Asif K., Mu, Weitong, Zhang, Shengming, Snyder, Solomon H., Wang, Rui·2008·Science

DOI 10.1126/science.1162667PMC PMC2749494

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Abstract

Studies of nitric oxide over the past two decades have highlighted the fundamental importance of gaseous signaling molecules in biology and medicine. The physiological role of other gases such as carbon monoxide and hydrogen sulfide (H2S) is now receiving increasing attention. Here we show that H2S is physiologically generated by cystathionine gamma-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H2S levels in the serum, heart, aorta, and other tissues. Mutant mice lacking CSE display pronounced hypertension and diminished endothelium-dependent vasorelaxation. CSE is physiologically activated by calcium-calmodulin, which is a mechanism for H2S formation in response to vascular activation. These findings provide direct evidence that H2S is a physiologic vasodilator and regulator of blood pressure.

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Hypertension in mice lacking the gene for endothelial nitric oxide synthase
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Authors: Yang, G., Wu, L., Jiang, B., Yang, W., Qi, J., Cao, K., Meng, Q., Mustafa, A. K., Mu, W., Zhang, S., Snyder, S. H., & Wang, R.
Affiliations: Johns Hopkins University (US)
Corresponding author: Wu, Lingyun
Snyder, Solomon H.
Wang, Rui
ORCID: Yang, Guangdong
Yang, Wei
Qi, Jiansong
Cao, Kun
Meng, Qinghe
Zhang, Shengming
Snyder, Solomon H.
Wang, Rui
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2008-10-24
Volume: 322
Issue: 5901
Pages: 587-590
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1162667
PMC: PMC2749494
OpenAlex: W2054064167
Cited by: 2,310
References: 27
Citations by year: 2026: 37 · 2025: 84 · 2024: 89 · 2023: 104 · 2022: 135 · 2021: 148 · 2020: 151 · 2019: 162 · 2018: 145 · 2017: 169 · 2016: 163 · 2015: 188 · 2014: 173 · 2013: 147 · 2012: 134
FWCI: 43.76
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R37MH018501, MH-18501)
National Institute on Drug Abuse (DA 00074, K05DA000074)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords: hydrogen sulfide, cystathionine gamma-lyase, hypertension, vasorelaxation, endothelium-dependent relaxation, calcium/calmodulin signaling, gasotransmitters, blood pressure regulation
MeSH terms: Animals, Aorta, Blood Pressure, Calcium, Calmodulin, Cystathionine gamma-Lyase, Cysteine, Endothelium, Vascular, Homocysteine, Hydrogen Sulfide, Hypertension, Mesenteric Arteries, Myocardium, Oxidation-Reduction, Sulfides, Vasodilation, Methacholine Chloride, Mice, Knockout, Mice

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H 2 S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine γ-Lyase

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