151. H2S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine γ-Lyase
- Author
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Shengming Zhang, Guangdong Yang, Jiansong Qi, Asif K. Mustafa, Qinghe Meng, Weitong Mu, Solomon H. Snyder, Bo Jiang, Rui Wang, Wei Yang, Lingyun Wu, and Kun Cao
- Subjects
medicine.medical_specialty ,Cell signaling ,Mutant ,Vasodilation ,Blood Pressure ,Sulfides ,Article ,Nitric oxide ,chemistry.chemical_compound ,Mice ,Calmodulin ,Internal medicine ,medicine ,Animals ,Cysteine ,Hydrogen Sulfide ,Homocysteine ,Aorta ,Methacholine Chloride ,Mice, Knockout ,Multidisciplinary ,biology ,Chemistry ,Myocardium ,Cystathionine gamma-lyase ,Cystathionine gamma-Lyase ,Biological activity ,equipment and supplies ,Cystathionine beta synthase ,Mesenteric Arteries ,Blood pressure ,Endocrinology ,Hypertension ,biology.protein ,Calcium ,Endothelium, Vascular ,Oxidation-Reduction - 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 (H 2 S) is now receiving increasing attention. Here we show that H 2 S is physiologically generated by cystathionine γ-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H 2 S 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 H 2 S formation in response to vascular activation. These findings provide direct evidence that H 2 S is a physiologic vasodilator and regulator of blood pressure.
- Published
- 2008