Decreased Endogenous Hydrogen Sulfide Generation in Penile Tissues of Diabetic Rats with Erectile Dysfunction

J Sex Med. 2016 Mar;13(3):350-60. doi: 10.1016/j.jsxm.2016.01.002. Epub 2016 Feb 4.

Abstract

Introduction: Hydrogen sulfide (H2S) is an endogenous gasotransmitter. The levels of H2S-generating enzyme expression and endogenous H2S production in diabetic rats with erectile dysfunction (ED) remain unknown. The aim of this study was to investigate the expression of the H2S-generating enzymes and endogenous production of H2S in penile tissues of diabetic ED rats.

Methods: Experimental rats were randomly divided into normal control group, apomorphine (APO)-positive group and APO-negative group. Primary rat corpus cavernosum smooth muscle cells (CCSMCs) and aortic endothelial cells (AECs) were isolated and cultured in vitro under 3 different conditions: normal glucose (NG) condition, high glucose (HG) condition, and osmotic control (OC) condition.

Main outcome measures: Erectile function; H2S concentrations in plasma or penile tissues; expression of H2S-generating enzymes and endogenous H2S production in penile tissues, CCSMCs, and AECs.

Results: Erectile function was significantly decreasedin the APO-negative group. In addition to significantly decreased expression of cysteine aminotransferase (CAT), d-amino acid oxidase (DAO), and 3-mercaptopyruvate sulfurtransferase (3-MST), the H2S concentrations in plasma and penile tissues and endogenous H2S production were significantly decreased in the APO-negative group. Endogenous H2S production by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) decreased to the same levels in the APO-negative and APO-positive groups as that in the normal control group. However, CBS and CSE expression remained unchanged in the 3 groups. Under HG conditions, H2S-generating enzyme expression in AECs did not change, while CAT, DAO, and 3-MST expression in CCSMCs was significantly decreased. In both cell types, H2S production by these enzymes was decreased in the HG group.

Conclusion: Endogenous H2S production was significantly decreased in the diabetic ED rats' penile tissues due to downregulated expression of the CAT/3-MST and DAO/3-MST pathways and low activities of CBS and CSE.

Keywords: Aortic Endothelial Cells; Corpus Cavernosum Smooth Muscle Cells; Erectile Dysfunction; Hydrogen Sulfide; Penile Tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cystathionine beta-Synthase / metabolism*
  • Cystathionine gamma-Lyase / metabolism*
  • Cysteine / analogs & derivatives
  • Diabetes Mellitus, Experimental / metabolism*
  • Endothelial Cells / metabolism
  • Erectile Dysfunction / pathology*
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Male
  • Neural Pathways / drug effects
  • Penis / pathology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • 3-mercaptopyruvic acid
  • Cystathionine beta-Synthase
  • Cystathionine gamma-Lyase
  • Cysteine
  • Hydrogen Sulfide