Hydrogen Sulfide as an Endothelium-Derived Hyperpolarizing Factor in Rodent Mesenteric Arteries

To the Editor:We read with interest the article by Mustafa et al1 in Circulation Research in which the authors suggest that hydrogen sulfide is a major endothelium-derived hyperpolarizing factor (EDHF) that generates endothelial and vascular myocyte hyperpolarization and relaxation by predominantly activating ATP-sensitive potassium channels (KATP) through cysteine S-sulfhydration. As previously reported by many groups, Mustafa et al1 confirm that endothelium-dependent cholinergic relaxations in murine mesenteric artery are minimally affected by combined inhibition of nitric oxide synthase and cyclooxygenase (L-NAME plus indomethacin), observations that are consistent with underlying EDHF-dependent mechanisms. However, it is important to stress that these data do not indicate that nitric oxide and prostacyclin pathways are poorly implicated because ACh-induced relaxations involve various overlapping endothelial mechanisms such that …