Acidic extracellular ph increases endothelin-i secretion by human endothelial cells of glomerular but not aortic origin

Wesson De Wesson, J. Simoni, D. F. Green

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2 Scopus citations


Endothelin-1 (ET-1) increases NHE-3 activity in renal epithelia, suggesting that this endothelial cell product might modulate renal acidification. Thus, acid extracellular pH might augment ET-1 release from renal microvascular endothelial cells in vivo, thereby increasing H secretion by adjacent epithelial cells. We investigated the effect of extracellular pH on ET-1 secretion by human glomerular endothelial cells (HGECs) and by endothelial cells of non-renal origin, human aortic endothelial cells (HAECs). Both cell types were grown to confluence in 6-well plates, exposed to serum-free media for 24 h, then switched to either control, acid, or alkaline serum-free media for 12 h in which ET-1 was measured by RIA after column extraction. Standard growth media pH was 7. 2 after equilibration with 5% CO2 at 37° C and so was made the pH of control media. Acid and alkaline media pH was 7. 0 and 7. , respectively. The 12 h media contained HEPES and TRIS buffers to maintain the assigned pH. HGECs exposed to the acid media had higher ET-1 than control (423 ±43 vs. 161 ±24 pg/ml, p < 0. 004) but those exposed to the alkaline media (141 ±63 pg/ml, p = NS vs. control) did not. This comparison among the three media was not changed by trasylol, an inhibitor of ET-1 degradation, suggesting that altered ET-1 degradation did not explain the effects of acid and alkaline media. Phosphoramidon (104 M), an inhibitor of the conversion of big ET-1 to biologically active ET-, prevented the increased ET-1 induced in HGECs by acid media, suggesting that acid media induces ET1 synthesis. Interleukin-1 (5 ng/ml), a stimulator of ET-1 synthesis, increased ET-1 in HGECs exposed to control (303 ±19 vs. 161 ±24 pg/ml, p < 0. 02) but not to acid media (326 ±46 vs. 423 ±43 pg/ml, p = NS), showing that the two inducers of ET-1 secretion are not additive. HAECs exposed to control, acid, and alkaline media had similar ET-1 concentrations (415. ±4, 347 ±46, and 513 ±63 pg/ml, p = NS), showing that the indicated changes in extracellular pH do not influence ET-1 secretion by HAECs as for HGECs. The data show that acid extracellular pH induces increased ET-1 secretion by HGECs, suggest that this response is not characteristic of all endothelial cells, and support the hypothesis that renal endothelial cells modulate renal acidification by pH-regulated secretion of ET-1.

Original languageEnglish (US)
Pages (from-to)336a
JournalJournal of Investigative Medicine
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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