Targeting the endothelium by combining endothelin-1 antagonism and SGLT-2 inhibition: better together?

Clin Sci (Lond). 2024 Jun 5;138(11):687-697. doi: 10.1042/CS20240605.

Abstract

Endothelin A and B receptors, together with sodium-glucose cotransporter-2 (SGLT-2) channels are important targets in improving endothelial function and intervention with inhibitors has been the subject of multiple mechanistic and clinical outcome trials over recent years. Notable successes include the treatment of pulmonary hypertension with endothelin receptor antagonists, and the treatment of heart failure and chronic kidney disease with SGLT-2 inhibitors. With distinct and complementary mechanisms, in this review, we explore the logic of combination therapy for a number of diseases which have endothelial dysfunction at their heart.

Keywords: chronic kidney disease; cirrhosis; endothelial dysfunction; endothelins.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Therapy, Combination
  • Endothelin Receptor Antagonists / therapeutic use
  • Endothelin-1* / metabolism
  • Endothelium, Vascular* / drug effects
  • Endothelium, Vascular* / metabolism
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology
  • Humans
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Endothelin-1
  • Endothelin Receptor Antagonists