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

  • Ion channels, receptors and transporters
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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 H2S on shear stress-mediated dilation of isolated mouse coronary arteries. In these vessels, Na2S 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 Na2S, suggesting that H2S 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/cm2) and produced graded dilatory responses, but such effects were diminished in the presence of 100 μM Na2S. 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 H2S signaling. Na2S 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 H2S 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 H2S through inhibition of NO generation.

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Acknowledgements

This work was supported by the National Institute of Health (HL080118, HL074180), and by the American Diabetes Association (ADA-JFA-07-39 and 1-12-BS-119). Address Correspondence to: Hon-Chi Lee, M.D., Ph.D. Email lee.honchi@mayo.edu or Qiang Chai Ph.D. Email qiang.chai@hotmail.com

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All authors disclosed that they do not have any potential conflict of interest.

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Chai, Q., Lu, T., Wang, XL. et al. Hydrogen sulfide impairs shear stress-induced vasodilation in mouse coronary arteries. Pflugers Arch - Eur J Physiol 467, 329–340 (2015). https://doi.org/10.1007/s00424-014-1526-y

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  • DOI: https://doi.org/10.1007/s00424-014-1526-y

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