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Paradoxical vasoconstrictive effects of H2S on shear stress‐mediated vasodilation

We examined the role of H2S on shear stress‐mediated dilation of isolated mouse coronary arteries. Na2S produced concentration‐dependent dilation in these vessels, which was significantly inhibited by iberiotoxin. BK currents in mouse coronary smooth muscle cells were directly activated by Na2S, suggesting H2S produced vasodilation through BK 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), producing 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. Using cultured bovine aortic endothelial cells, eNOS activity was inhibited by Na2S. 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. (Supported by grants from NIH)