H 2 S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine γ-Lyase
Open accessAbstract
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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Several enzymatic and non-enzymatic sources contribute to the existing pool of sulfide in circulation and tissues, with a purportedly essential role in blood pressure regulation.
“Several enzymatic and non-enzymatic sources have been identified to contribute to the existing pool of sulfide in circulation and tissues [1][2][3], with a purportedly essential role in blood pressure regulation [4].”
From On the chemical biology of the nitrite/sulfide interaction (2015) · cites this paper as [4]
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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
- Venue
- Science
- Published
- 2008-10-24
- Volume
- 322
- Issue
- 5901
- Pages
- 587-590
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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 › 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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