Reduced extracellular pH increases endothelin-1 secretion by human renal microvascular endothelial cells

J Clin Invest. 1998 Feb 1;101(3):578-83. doi: 10.1172/JCI854.


Because dietary acid increases renal secretion of endothelin-1 (ET-1) which is synthesized by renal microvascular endothelium, we examined if reduced extracellular pH increases ET-1 secretion by cultured human renal microvascular endothelial cells (RMVECs). Confluent cells were exposed to serum-free media for 24 h, then incubated in either control, acid, or alkaline serum-free media for 12 h. Standard growth media pH was 7.2 after equilibration with 5% CO2 at 37 degrees C and was made the pH of control media. Acid and alkaline media pH were 7.0 and 7.4, respectively. Added Hepes and Tris maintained all assigned pHs. Media ET-1 measured by RIA after column extraction was higher for RMVECs exposed to acid compared with control media (170.0+/-17.1 vs. 64.6+/-9.6 pM, P < 0.004) but those exposed to alkaline media (56.6+/-25.1 pM, P = NS vs. control) were not. Human aortic endothelial cells exposed to control, acid, and alkaline media had similar ET-1 (166.6+/-18.1, 139.3+/-18.5, and 205.9+/-25.3 pM, P = NS). The data show acid-stimulated ET-1 secretion by RMVECs but not aortic endothelial cells, demonstrating a new environmental factor that influences ET-1 secretion by renal microvascular endothelium and thereby possibly modulates endothelin-dependent processes in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aorta / cytology
  • Aorta / metabolism
  • Cell Line
  • Cells, Cultured
  • Culture Media
  • Endothelin-1 / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Extracellular Space
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / metabolism*


  • Culture Media
  • Endothelin-1