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Science 24 October 2008:
Vol. 322. no. 5901, pp. 587 - 590
DOI: 10.1126/science.1162667
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Reports

H2S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine {gamma}-Lyase

Guangdong Yang,1,5 Lingyun Wu,2* Bo Jiang,1 Wei Yang,1 Jiansong Qi,1 Kun Cao,1 Qinghe Meng,3 Asif K. Mustafa,4 Weitong Mu,4,6 Shengming Zhang,5 Solomon H. Snyder,4* Rui Wang1,5*

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.

1 Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
2 Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
3 Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
4 Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
5 Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada.
6 Department of Medicine, Gastroenterology Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* To whom correspondence should be addressed. E-mail: rwang{at}lakeheadu.ca (R.W.), lily.wu{at}usask.ca (L.W.), or ssnyder{at}jhmi.edu (S.H.S.).

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