Endothelin increases NO-dependent cGMP production in isolated glomeruli but not in mesangial cells

I. Tack, E. Marin Castano, C. Pêcher, F. Praddaude, J. L. Bascands, G. Bompart, J. L. Ader, J. P. Girolami

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The ability of endothelins (ETs) to modulate nitric oxide-dependent glomerular guanosine 3'-5'-cyclic monophosphate (cGMP) production has recently been reported. The aim of this study was to directly confirm, using an antagonist, the involvement of the ETa receptor subtype and to investigate the potential role of mesangial cells (MC) in this ET-induced cGMP production. In glomeruli freshly isolated from rats, endothelin-3 (ET-3) induced a dose-dependent increase in cGMP content. This increase was inhibited by N(G)-monomethyl-L-arginine (L-NMMA) and methylene blue and was calcium dependent. Moreover the effect of ET-3 was prevented by two ET(B)selective receptor antagonists, BQ-788 and IRL-1038, but not by BQ-123, an ET(A)-selective receptor antagonist. It therefore appeared that ET-3 stimulates the glomerular constitutive NO pathway through activation of the ET(B) receptor subtype. In contrast, ET-3 and calcium ionophore had no effect on cGMP formation in cultured MC, whereas incubation with sodium nitroprusside resulted in an ~50-fold increase in the intraeellular content of cGMP. However, ET-3 induced a dose-dependent rise in free MC cytosolic calcium that was abolished by an ET(B) antagonist. Moreover, both ETA and ETa receptors mRNA were expressed in primary cultures of MC. Finally, we failed to detest the presence of constitutive NO synthase (NOS), as demonstrated by the absence of L-citrulline forming activity and of the mRNA encoding for endothelial NOS, whereas they were present in isolated glomeruli. These data indicate that MC, despite the fact that they express ET(B) receptors, are not involved in glomerular NO production induced by exposure to ET-3, because they do not express constitutive NO synthase.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume272
Issue number1 41-1
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Endothelin-3
Mesangial Cells
Endothelins
Nitric Oxide Synthase
Endothelin B Receptors
Calcium
omega-N-Methylarginine
Citrulline
Messenger RNA
Calcium Ionophores
Guanosine
Methylene Blue
Nitroprusside
Arginine
Cultured Cells
Nitric Oxide

Keywords

  • Endothelin receptors
  • Glomerulus
  • Guanosine 3',5'- cyclic monophosphate
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology

Cite this

Tack, I., Marin Castano, E., Pêcher, C., Praddaude, F., Bascands, J. L., Bompart, G., ... Girolami, J. P. (1997). Endothelin increases NO-dependent cGMP production in isolated glomeruli but not in mesangial cells. American Journal of Physiology - Renal Physiology, 272(1 41-1).

Endothelin increases NO-dependent cGMP production in isolated glomeruli but not in mesangial cells. / Tack, I.; Marin Castano, E.; Pêcher, C.; Praddaude, F.; Bascands, J. L.; Bompart, G.; Ader, J. L.; Girolami, J. P.

In: American Journal of Physiology - Renal Physiology, Vol. 272, No. 1 41-1, 01.01.1997.

Research output: Contribution to journalArticle

Tack, I, Marin Castano, E, Pêcher, C, Praddaude, F, Bascands, JL, Bompart, G, Ader, JL & Girolami, JP 1997, 'Endothelin increases NO-dependent cGMP production in isolated glomeruli but not in mesangial cells', American Journal of Physiology - Renal Physiology, vol. 272, no. 1 41-1.
Tack I, Marin Castano E, Pêcher C, Praddaude F, Bascands JL, Bompart G et al. Endothelin increases NO-dependent cGMP production in isolated glomeruli but not in mesangial cells. American Journal of Physiology - Renal Physiology. 1997 Jan 1;272(1 41-1).
Tack, I. ; Marin Castano, E. ; Pêcher, C. ; Praddaude, F. ; Bascands, J. L. ; Bompart, G. ; Ader, J. L. ; Girolami, J. P. / Endothelin increases NO-dependent cGMP production in isolated glomeruli but not in mesangial cells. In: American Journal of Physiology - Renal Physiology. 1997 ; Vol. 272, No. 1 41-1.
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abstract = "The ability of endothelins (ETs) to modulate nitric oxide-dependent glomerular guanosine 3'-5'-cyclic monophosphate (cGMP) production has recently been reported. The aim of this study was to directly confirm, using an antagonist, the involvement of the ETa receptor subtype and to investigate the potential role of mesangial cells (MC) in this ET-induced cGMP production. In glomeruli freshly isolated from rats, endothelin-3 (ET-3) induced a dose-dependent increase in cGMP content. This increase was inhibited by N(G)-monomethyl-L-arginine (L-NMMA) and methylene blue and was calcium dependent. Moreover the effect of ET-3 was prevented by two ET(B)selective receptor antagonists, BQ-788 and IRL-1038, but not by BQ-123, an ET(A)-selective receptor antagonist. It therefore appeared that ET-3 stimulates the glomerular constitutive NO pathway through activation of the ET(B) receptor subtype. In contrast, ET-3 and calcium ionophore had no effect on cGMP formation in cultured MC, whereas incubation with sodium nitroprusside resulted in an ~50-fold increase in the intraeellular content of cGMP. However, ET-3 induced a dose-dependent rise in free MC cytosolic calcium that was abolished by an ET(B) antagonist. Moreover, both ETA and ETa receptors mRNA were expressed in primary cultures of MC. Finally, we failed to detest the presence of constitutive NO synthase (NOS), as demonstrated by the absence of L-citrulline forming activity and of the mRNA encoding for endothelial NOS, whereas they were present in isolated glomeruli. These data indicate that MC, despite the fact that they express ET(B) receptors, are not involved in glomerular NO production induced by exposure to ET-3, because they do not express constitutive NO synthase.",
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AU - Tack, I.

AU - Marin Castano, E.

AU - Pêcher, C.

AU - Praddaude, F.

AU - Bascands, J. L.

AU - Bompart, G.

AU - Ader, J. L.

AU - Girolami, J. P.

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AB - The ability of endothelins (ETs) to modulate nitric oxide-dependent glomerular guanosine 3'-5'-cyclic monophosphate (cGMP) production has recently been reported. The aim of this study was to directly confirm, using an antagonist, the involvement of the ETa receptor subtype and to investigate the potential role of mesangial cells (MC) in this ET-induced cGMP production. In glomeruli freshly isolated from rats, endothelin-3 (ET-3) induced a dose-dependent increase in cGMP content. This increase was inhibited by N(G)-monomethyl-L-arginine (L-NMMA) and methylene blue and was calcium dependent. Moreover the effect of ET-3 was prevented by two ET(B)selective receptor antagonists, BQ-788 and IRL-1038, but not by BQ-123, an ET(A)-selective receptor antagonist. It therefore appeared that ET-3 stimulates the glomerular constitutive NO pathway through activation of the ET(B) receptor subtype. In contrast, ET-3 and calcium ionophore had no effect on cGMP formation in cultured MC, whereas incubation with sodium nitroprusside resulted in an ~50-fold increase in the intraeellular content of cGMP. However, ET-3 induced a dose-dependent rise in free MC cytosolic calcium that was abolished by an ET(B) antagonist. Moreover, both ETA and ETa receptors mRNA were expressed in primary cultures of MC. Finally, we failed to detest the presence of constitutive NO synthase (NOS), as demonstrated by the absence of L-citrulline forming activity and of the mRNA encoding for endothelial NOS, whereas they were present in isolated glomeruli. These data indicate that MC, despite the fact that they express ET(B) receptors, are not involved in glomerular NO production induced by exposure to ET-3, because they do not express constitutive NO synthase.

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