Dup 753 is a potent nonpeptide antagonist of angiotensin ii receptors in isolated perfused rat kidney and cultured renal cells

B. M A Fontoura, D. R. Nussenzveig, P. B M W M Timmermans, T. Maack

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

In the present study we investigated the antagonist action of DuP 753 {2 - n - butyl - 4 - chloro - 5 - hydroxy­methyl - 1 - [2' - (1H - tetrazol - 5 - yl)biphenyl - 4-yl) methyljimidazole, potassium salt) on angiotensin II (All) binding and vascular effects in the isolated perfused rat kidney. In addition, we determined binding of DuP 753 in cultured glomerular mesan­gial cells and renomedullary interstitial cells. In the isolated kidney, DuP 753 fully displaced All from its specific binding sites with high affinity (IC^ = 200 nmol/L) and antagonized the vasoconstrictive effect of All in a dose-related manner with an ED^ of 170 nmol/L. These effects of DuP 753 were qual­itatively similar to those of saralasin and the antag­onist effect of DuP 753 on All-induced renal vaso­constriction was fully overcome by excess AIL DuP 753 had no effect on its own on renal vascular re­sistance. In cultured glomerular mesangial cells and renomedullary interstitial cells, DuP 753 fully in­hibited the specific binding of [125I]-Sar-AII at /miol/L with IC50s of 6.7 and 11 nmol/L for glo­merular mesangial cells and renomedullary inter­stitial cells, respectively. The present results dem­onstrate that a novel imidazole derivative, DuP 753, is a powerful non-peptide antagonist of angiotensin receptors in isolated perfused rat kidney and in cultured glomerular mesangial and renomedullary interstitial cells. Am J Hypertens 1991;4:303S-308S.

Original languageEnglish (US)
Pages (from-to)303s-308s
JournalAmerican Journal of Hypertension
Volume4
Issue number4
DOIs
StatePublished - Apr 1991

Keywords

  • Angiotensin II binding
  • Glomerular mesangial cells
  • Isolated per­fused rat kidney
  • Renal vasoconstriction
  • Renomedullary interstitial cells

ASJC Scopus subject areas

  • Internal Medicine

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