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

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-I secretion bl; 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-I secretion by RMVECs but not aortic endothelial cells, demonstrating a new environmental factor that influences ET-I secretion by renal microvascular endothelium and thereby possibly modulates endothelin-dependent processes in vivo.