Hydrogen sulfide impairs shear stress-induced vasodilation in mouse coronary arteries

Qiang Chai, Tong D Lu, Xaio Li Wang, Hon Chi Lee

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Hydrogen sulfide has emerged as an important endothelium-dependent vasodilator, but its role in shear stress-mediated dilation of coronary arteries is unclear. We examined the role of H<inf>2</inf>S on shear stress-mediated dilation of isolated mouse coronary arteries. In these vessels, Na<inf>2</inf>S produced concentration-dependent dilation, which was significantly inhibited by iberiotoxin and by 4-aminopyridine. In addition, BK and Kv currents in mouse coronary smooth muscle cells were directly activated by Na<inf>2</inf>S, suggesting that H<inf>2</inf>S produced vasodilation through BK and Kv channel activation. Using a pressure servo controller system, freshly isolated mouse coronary arteries were subjected to physiological levels of shear stress (1 to 25 dynes/cm<sup>2</sup>) and produced graded dilatory responses, but such effects were diminished in the presence of 100 μM Na<inf>2</inf>S. Pre-incubation with the cystathionine γ-lyase inhibitor, d,l-propargylglycine (PPG), resulted in a paradoxical augmentation of shear stress-mediated vasodilation. However, in the presence of L-NAME or in coronary arteries from eNOS knockout mice, PPG inhibited shear stress-mediated vasodilation, suggesting an interaction between NO and H<inf>2</inf>S signaling. Na<inf>2</inf>S inhibited eNOS activity in cultured mouse aortic endothelial cells and reduced the level of phospho-eNOS(serine 1177). These results suggest that both NO and H<inf>2</inf>S are important shear stress-mediated vasodilators in mouse coronary arteries but there is a complex interaction between these two signaling pathways that results in paradoxical vasoconstrictive effects of H<inf>2</inf>S through inhibition of NO generation.

Original languageEnglish (US)
Pages (from-to)329-340
Number of pages12
JournalPflugers Archiv European Journal of Physiology
Volume467
Issue number2
DOIs
StatePublished - 2014

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Keywords

  • BK channel
  • H<inf>2</inf>S
  • Mouse coronary artery
  • NO
  • Shear stress

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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