title: Hydrogen sulfide impairs shear stress-induced vasodilation in mouse coronary arteries.
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/cm(2)) 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.
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, 55905, USA, qiang.chai@hotmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chai
authors.forename: Tong
authors.initials: T
authors.lastname: Lu
authors.forename: Xaio-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Hon-Chi
authors.initials: HC
authors.lastname: Lee
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011312:Pressure; D013440:Sulfides / Q000494:pharmacology; D014664:Vasodilation
chemical_list: D000480:Alkynes; D010455:Peptides; D026902:Potassium Channel Blockers; D013440:Sulfides; D009569:Nitric Oxide; C009055:propargylglycine; C064719:iberiotoxin; D015761:4-Aminopyridine; D052250:Nitric Oxide Synthase Type III; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester; C033479:sodium sulfide; D006862:Hydrogen Sulfide