Cystathionine γ-Lyase-Produced Hydrogen Sulfide Controls Endothelial NO Bioavailability and Blood Pressure

Hydrogen sulfide (H₂S) and NO are important gasotransmitters, but how endogenous H₂S affects the circulatory system has remained incompletely understood. Here, we show that CTH or CSE (cystathionine γ-lyase)-produced H₂S scavenges vascular NO and controls its endogenous levels in peripheral arteries, which contribute to blood pressure regulation. Furthermore, eNOS (endothelial NO synthase) and phospho-eNOS protein levels were unaffected, but levels of nitroxyl were low in CTH-deficient arteries, demonstrating reduced direct chemical interaction between H₂S and NO. Pretreatment of arterial rings from CTH-deficient mice with exogenous H₂S donor rescued the endothelial vasorelaxant response and decreased tissue NO levels. Our discovery that CTH-produced H₂S inhibits endogenous endothelial NO bioavailability and vascular tone is novel and fundamentally important for understanding how regulation of vascular tone is tailored for endogenous H₂S to contribute to systemic blood pressure function.