H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase.

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.

• Authors: Guangdong Yang, Lingyun Wu, Bo Jiang, Wei Yang, Jiansong Qi, Kun Cao, Qinghe Meng, Asif K Mustafa, Weitong Mu, Shengming Zhang, Solomon H Snyder, Rui Wang
• Journal: Science (New York, N.Y.) (Science) Vol. 322 Issue 5901 Pg. 587-90 (Oct 24 2008) ISSN: 1095-9203 [Electronic] United States
• PMID: 18948540 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Calmodulin
• Sulfides
• Homocysteine
• Methacholine Chloride
• Cystathionine gamma-Lyase
• sodium bisulfide
• Cysteine
• Calcium
• Hydrogen Sulfide

Topics

• Animals
• Aorta (metabolism)
• Blood Pressure
• Calcium (metabolism)
• Calmodulin (metabolism)
• Cystathionine gamma-Lyase (deficiency, genetics, metabolism)
• Cysteine (blood)
• Endothelium, Vascular (metabolism)
• Homocysteine (blood)
• Hydrogen Sulfide (blood, metabolism)
• Hypertension (physiopathology)
• Mesenteric Arteries (physiology)
• Methacholine Chloride (pharmacology)
• Mice
• Mice, Knockout
• Myocardium (metabolism)
• Oxidation-Reduction
• Sulfides (pharmacology)
• Vasodilation