Hypertension and Aging Affect Liver Sulfur Metabolism in Rats

Cells. 2021 May 18;10(5):1238. doi: 10.3390/cells10051238.

Abstract

Hypertension and age are key risk factors for cardiovascular morbidity and mortality. Hydrogen sulfide (H2S), a gaseous transmitter, contributes significantly to regulating arterial blood pressure and aging processes. This study evaluated the effects of hypertension and aging on the hepatic metabolism of sulfur-containing compounds, the activity of the enzymes involved in sulfur homeostasis, and the liver's ability to generate H2S. Livers isolated from 16- and 60-week-old normotensive Wistar Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR) were used to evaluate gene expression using RT-PCR, and the activity of enzymes participating in H2S metabolism, including thiosulfate sulfurtransferase (rhodanese; TST), cystathionine gamma-lyase (CTH), and 3-mercaptopyruvate sulfurtransferase (MPST). The levels of cysteine, cystine, reduced and oxidized glutathione were measured using RP-HPLC. SHR livers from both age groups showed a higher capacity to generate H2S than livers from WKY. The gene expression and activity of enzymes involved in sulfur metabolism differed between WKY and SHR, and between the age groups. For example, 16-week-old SHR had significantly higher activity of TST than 16-week-old WKY. Furthermore, differences between younger and older WKY rats in the expression and/or activity of TST and MPST were present. In conclusion, our study shows that arterial hypertension and aging affect hepatic sulfur metabolism and H2S production in rats. These findings pave the way for interventional studies evaluating a potential causal relation between liver sulfur metabolism, hypertension and aging.

Keywords: 3-mercaptopyruvate sulfurtransferase; aging; cystathionine gamma-lyase; hydrogen sulfide; hypertension; liver; thiosulfate sulfurtransferase (rhodanese).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / metabolism*
  • Animals
  • Arterial Pressure*
  • Cystathionine gamma-Lyase / genetics
  • Cystathionine gamma-Lyase / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic
  • Hydrogen Sulfide / metabolism*
  • Hypertension / genetics
  • Hypertension / metabolism*
  • Hypertension / physiopathology*
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sulfurtransferases / genetics
  • Sulfurtransferases / metabolism
  • Thiosulfate Sulfurtransferase / genetics
  • Thiosulfate Sulfurtransferase / metabolism

Substances

  • Sulfurtransferases
  • Thiosulfate Sulfurtransferase
  • 3-mercaptopyruvate sulphurtransferase
  • Cystathionine gamma-Lyase
  • Hydrogen Sulfide