High Glucose Induces The Release Of Endothelin-1 Through The Inhibition Of Hydrogen Sulfide Production In Huvecs

Hydrogen sulfide (H2S) has recently been identified as an endogenous gaseous signaling molecule. In the vascular system, the formation of H2S is catalyzed by cystathionine gamma-lyase (CSE). Previous studies have demonstrated the protective effects of H2S on ischemic injury in various types of tissue. However little is known about the role of H2S in diabetes-associated vascular diseases. Thus, the aim of the present study was to examine the possible role of H2S in high glucose-induced vascular dysfunction, and to explore the underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were isolated from human umbilical veins. The levels of H2S following treatment with various levels of glucose were determined and the secretion of endothelin-1 (ET-1) was measured by ELISA. The mRNA and protein expression of CSE in the HUVECs was determined by real-time RT-PCR and western blot analysis, respectively. Treatment with high glucose (25 mmol/1) for 48 h significantly increased the secretion of ET-1 by HUVECs, with the concomitant suppression of H2S production and CSE protein expression. The increase in exogenous H2S levels through the administration of sodium hydrosulfide (NaHS) attenuated the high glucose-induced downregulation of CSE protein expression, and significantly inhibited the secretion of ET-1. These results suggest that the downregulation of CSE protein expression and the subsequent decrease in H2S production play a role in high glucose-induced vascular dysfunction possibly by increasing the secretion of ET-1 by endothelial cells.