Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery.
This study aimed to test these hypotheses: cystathionine gamma-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H(2)S), and H(2)S relaxes a human artery. H(2)S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H(2)S 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 H(2)S, and the H(2)S production was inhibited by dl-propargylglycine, an inhibitor of CSE. We also showed that H(2)S 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 H(2)S, and that higher concentrations of H(2)S relax human arteries, in part by opening K(ATP) channels. Low concentrations of H(2)S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H(2)S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.
Webb
George D
GD
Department of Molecular Physiology and Biophysics, University of Vermont, College of Medicine, Health Science Research Facility Building, Burlington, VT 05405, USA. george.webb@uvm.edu
Lim
Lay Har
LH
Oh
Vernon M S
VM
Yeo
Soh Bee
SB
Cheong
Yoke Ping
YP
Ali
Muhammed Yusuf
MY
El Oakley
Reida
R
Lee
Chuen Neng
CN
Wong
Poo Sing
PS
Caleb
Michael G
MG
Salto-Tellez
Manuel
M
Bhatia
Madhav
M
Chan
Edwin S Y
ES
Taylor
Elizabeth A
EA
Moore
Philip K
PK
D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008323:Mammary Arteries / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism
D014665:Vasodilator Agents; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide