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

Abstract

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