Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: a new possible role of PPARgamma on vascular endothelial function

Biochem Biophys Res Commun. 1999 Jan 27;254(3):757-63. doi: 10.1006/bbrc.1998.0126.


We examined the effect of troglitazone on immunoreactive endothelin-1 (ET-1) secretion from cultured bovine vascular endothelial cells (bVECs). Insulin (10(-9)-10(-7) M) stimulated ET-1 secretion in a dose-dependent fashion without any kinetic change. Troglitazone (1-20 microM) dose-dependently inhibited both spontaneous and insulin-stimulated ET-1 secretion. This inhibitory effect of troglitazone was associated with reduced ET-1 mRNA levels. Addition of indomethacin (100 microM) or Nw-nitro-l-arginine methyl ester (1 mM) and downregulation of protein kinase C by prolonged pretreatment of the cells with a phorbol ester, 12-O-tetradecanoylphorbol 13-acetate, did not affect the inhibitory effect of troglitazone at concentrations up to 10 microM. Troglitazone did not change the intracellular Ca2+ concentration stimulated by angiotensin II (10 microM). Other PPARgamma ligands, pioglitazone (1-10 microM) and 15-deoxy-delta 12, 14-prostaglandin J2 (1-10 microM), but not a PPARalpha ligand, bezafibrate (1-10 microM), dose-dependently suppressed spontaneous ET-1 secretion from bVECs. These results, taken together, suggest that troglitazone inhibits ET-1 mRNA expression and secretion in bVECs possibly through activation of PPARgamma. This inhibition may contribute to the hypotensive effect of troglitazone in insulin-resistant subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Chromans / metabolism
  • Chromans / pharmacology*
  • Endothelin-1 / antagonists & inhibitors*
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Pioglitazone
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / metabolism
  • Prostaglandin D2 / pharmacology
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Thiazoles / metabolism
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Transcription Factors / metabolism*
  • Troglitazone


  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Chromans
  • Endothelin-1
  • Hypoglycemic Agents
  • Insulin
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Troglitazone
  • Prostaglandin D2
  • Pioglitazone