Cystathionine γ-lyase-produced hydrogen sulfide controls endothelial NO bioavailability and blood pressure

Hydrogen sulfide (H(2)S) and NO are important gasotransmitters, but how endogenous H(2)S affects the circulatory system has remained incompletely understood. Here, we show that CTH or CSE (cystathionine γ-lyase)-produced H(2)S 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 H(2)S and NO. Pretreatment of arterial rings from CTH-deficient mice with exogenous H(2)S donor rescued the endothelial vasorelaxant response and decreased tissue NO levels. Our discovery that CTH-produced H(2)S inhibits endogenous endothelial NO bioavailability and vascular tone is novel and fundamentally important for understanding how regulation of vascular tone is tailored for endogenous H(2)S to contribute to systemic blood pressure function.