Endothelin-1 inhibits cytokine-stimulated transcription of inducible nitric oxide synthase in glomerular mesangial cells

Kidney International
K F BeckR B Sterzel

Abstract

Endothelin-1 (ET-1) is a potent vasoconstrictor while nitric oxide (NO) has strong vasodilatory effects. Recent studies have indicated that vasoconstrictors and NO may mutually modulate their production and/or activity, thus regulating each other in the context of microcirculatory maintenance. We examined the question whether ET-1 may affect NO formation by controlling the expression of the inducible isoform of the NO synthase (iNOS) in cultured rat glomerular mesangial cells (MCs), as induced by the inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) plus interleukin-1 beta (IL-1 beta). We found that ET-1 in MCs markedly reduced cytokine-induced NO production (measured as stable NO2-) and inhibited the expression of iNOS mRNA (Northern blot analysis) and of iNOS protein (Western blotting). Inhibition of cytokine-stimulated iNOS mRNA expression by ET-1 was almost complete at the level of gene transcription while post-transcriptional effects were not detected. The ETA receptor antagonist BQ-123 blocked the inhibitory effect of ET1. The ETA agonist sarafotoxin 6b (S6b) inhibited, while the ETB agonist-sarafotoxin 6c (S6c) did not inhibit cytokine-initiated iNOS transcription in MCs. The results demonstrate that ET-1 c...Continue Reading

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Citations

Jul 23, 2003·Experimental Eye Research·Renyi WuIvan O Haefliger
Jan 21, 2011·Physiological Reviews·Donald E KohanDavid M Pollock
Dec 31, 1997·American Journal of Respiratory and Critical Care Medicine·P T MurrayJ G Umans
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Sep 5, 2003·American Journal of Physiology. Renal Physiology·Andrey Sorokin, Donald E Kohan
Nov 6, 2020·Cellular Signalling·Karl-Friedrich Beck, Josef Pfeilschifter
Jan 5, 2000·Journal of the American Society of Nephrology : JASN·Roland VeelkenR Bernd Sterzel
Mar 7, 2000·Journal of the American Society of Nephrology : JASN·Sebastian WalpenJosef Pfeilschifter
Jul 1, 1997·Kidney International·S AielloG Remuzzi
Jan 1, 1997·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·D E Kohan

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