Received for publication October 25, 2007.
Revised November 18, 2007.
Accepted for publication November 19, 2007.

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

Abstract

This study aimed to test these hypotheses: cystathionine gamma-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 RT-PCR, 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 pre-relaxed 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.

Key words: CSE, artery, cystathionine gamma-lyase, hydrogen sulfide, internal mammary artery, internal thoracic artery

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