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

Hypertension. 2018 Jun;71(6):1210-1217. doi: 10.1161/HYPERTENSIONAHA.117.10562. Epub 2018 Apr 30.

Abstract

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.

Keywords: animals; hydrogen sulfide; hypertension; nitric oxide; nitric oxide synthase type III.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Availability
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Cystathionine gamma-Lyase / pharmacology*
  • Disease Models, Animal
  • Hydrogen Sulfide / metabolism*
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / physiopathology
  • Mice
  • Nitric Oxide / metabolism*
  • Vasodilation / drug effects*

Substances

  • Nitric Oxide
  • Cystathionine gamma-Lyase
  • Hydrogen Sulfide