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CARDIOVASCULAR

Contractile and Vasorelaxant Effects of Hydrogen Sulfide and Its Biosynthesis in the Human Internal Mammary Artery

Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, Vermont (G.D.W.); Departments of Medicine (V.M.S.O., S.B.Y., E.A.T.), Pharmacology (L.H.L., Y.P.C., M.Y.A., M.B., P.K.M.), Surgery (M.G.C., R.E.O., C.N.L., P.S.W.), and Pathology (M.S.-T.), Office of Life Science Cardiovascular Biology Programme, National University of Singapore, Singapore; and Clinical Trials and Epidemiology Research Unit, Ministry of Health, Singapore (E.S.Y.C.)

This study aimed to test these hypotheses: cystathionine -lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H₂S), and H₂S relaxes a human artery. H₂S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H₂S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H₂S, and the H₂S production was inhibited by DL-propargylglycine, an inhibitor of CSE. We also showed that H₂S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of K_ATP channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H₂S, and that higher concentrations of H₂S relax human arteries, in part by opening K_ATP channels. Low concentrations of H₂S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H₂S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.

Address correspondence to: George Webb, Department of Molecular Physiology and Biophysics, University of Vermont, College of Medicine, Health Science Research Facility Building, Burlington, VT 05405. E-mail: george.webb{at}uvm.edu

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				L. Li, M. Whiteman, Y. Y. Guan, K. L. Neo, Y. Cheng, S. W. Lee, Y. Zhao, R. Baskar, C.-H. Tan, and P. K. Moore Characterization of a Novel, Water-Soluble Hydrogen Sulfide-Releasing Molecule (GYY4137): New Insights Into the Biology of Hydrogen Sulfide Circulation, May 6, 2008; 117(18): 2351 - 2360. [Abstract] [Full Text] [PDF]