Hydrogen sulfide-mediated endothelial function and the interaction with eNOS and PDE5A activity in human internal mammary arteries

Objective To investigate the role of hydrogen sulfide (H2S) in human internal mammary arteries (IMA) and its interaction with endothelial nitric oxide synthase (eNOS) and phosphodiesterase (PDE)5A activity. Methods Human IMA segments from patients undergoing coronary artery bypass grafting (CABG) were studied by myography for acetylcholine and sodium hydrosulfide (NaHS)-induced relaxation. Locations of 3-mercaptopyruvate sulfurtransferase (3-MPST) and cysteine aminotransferase (CAT) were examined immunohistochemically. Levels of H2S, eNOS, phosphorylated-eNOSser1177, and PDE5A were measured. Results In IMA segments from 47 patients, acetylcholine-induced relaxation (resistant to NG-nitro-L-arginine and indomethacin) was significantly attenuated by aminooxyacetic acid or L-aspartate (CAT inhibitors), iberiotoxin (large-conductance calcium-activated K+ channel blocker), TRAM-34 plus apamin (intermediate- and small-conductance Ca2+-activated K+ channel blockers) or glibenclamide (ATP-sensitive K+ channel blocker). 3-MPST and mitochondrial CAT were found in endothelial and smooth muscle cells while cytosolic CAT was located only in endothelial cells. Acetylcholine significantly increased the H2S levels. The H2S donor, NaHS, increased eNOS phosphorylation and down-regulated PDE5A. Conclusions Human conduit artery endothelium releases H2S under basal and stimulated conditions, involving the 3-MPST/CAT pathway, eNOS phosphorylation, PDE5A activity, and potassium channels. These findings may provide new therapeutic targets for treating vasospasm in CABG grafts and facilitate the development of new vasodilator drugs.