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

24 Citations (Scopus)

Abstract

In the present study we investigated the antagonist action of DuP 753 {2-n-butyl-4-chloro-5-hydroxy-methyl-1-[2'-(1H-tetrazol-5-yl)biphenyl -4-yl)methyl]imidazole, potassium salt} on angiotensin II (AII) 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 AII from its specific binding sites with high affinity (IC50 = 200 nmol/L) and antagonized the vasoconstrictive effect of AII in a dose-related manner with an ED50 of 170 nmol/L. These effects of DuP 753 were qualitatively similar to those of saralasin and the antagonist effect of DuP 753 on AII-induced renal vasoconstriction was fully overcome by excess AII. 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 1 μmol/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 angiotension II receptors in isolated perfused rat kidney and in cultured glomerular mesangial and renomedullary interstitial cells.

Original languageEnglish (US)
JournalAmerican Journal of Hypertension
Volume4
Issue number4 II SUPPL.
StatePublished - 1991

Fingerprint

Losartan
Angiotensin Receptor Antagonists
Cultured Cells
Kidney
Angiotensin II
Mesangial Cells
Saralasin
Vasoconstriction
Vascular Resistance
Inhibitory Concentration 50
Blood Vessels
Potassium
Salts
Binding Sites

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{02694058883d44f79b4711ea25bff4c9,
title = "DuP 753 is a potent nonpeptide antagonist of angiotensin II receptors in isolated perfused rat kidney and cultured renal cells",
abstract = "In the present study we investigated the antagonist action of DuP 753 {2-n-butyl-4-chloro-5-hydroxy-methyl-1-[2'-(1H-tetrazol-5-yl)biphenyl -4-yl)methyl]imidazole, potassium salt} on angiotensin II (AII) 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 AII from its specific binding sites with high affinity (IC50 = 200 nmol/L) and antagonized the vasoconstrictive effect of AII in a dose-related manner with an ED50 of 170 nmol/L. These effects of DuP 753 were qualitatively similar to those of saralasin and the antagonist effect of DuP 753 on AII-induced renal vasoconstriction was fully overcome by excess AII. 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 1 μmol/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 angiotension II receptors in isolated perfused rat kidney and in cultured glomerular mesangial and renomedullary interstitial cells.",
author = "Fontoura, {B. M A} and Nussenzveig, {D. R.} and Timmermans, {P. B M W M} and T. Maack",
year = "1991",
language = "English (US)",
volume = "4",
journal = "Journal of clinical hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "4 II SUPPL.",

}

TY - JOUR

T1 - DuP 753 is a potent nonpeptide antagonist of angiotensin II receptors in isolated perfused rat kidney and cultured renal cells

AU - Fontoura, B. M A

AU - Nussenzveig, D. R.

AU - Timmermans, P. B M W M

AU - Maack, T.

PY - 1991

Y1 - 1991

N2 - In the present study we investigated the antagonist action of DuP 753 {2-n-butyl-4-chloro-5-hydroxy-methyl-1-[2'-(1H-tetrazol-5-yl)biphenyl -4-yl)methyl]imidazole, potassium salt} on angiotensin II (AII) 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 AII from its specific binding sites with high affinity (IC50 = 200 nmol/L) and antagonized the vasoconstrictive effect of AII in a dose-related manner with an ED50 of 170 nmol/L. These effects of DuP 753 were qualitatively similar to those of saralasin and the antagonist effect of DuP 753 on AII-induced renal vasoconstriction was fully overcome by excess AII. 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 1 μmol/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 angiotension II receptors in isolated perfused rat kidney and in cultured glomerular mesangial and renomedullary interstitial cells.

AB - In the present study we investigated the antagonist action of DuP 753 {2-n-butyl-4-chloro-5-hydroxy-methyl-1-[2'-(1H-tetrazol-5-yl)biphenyl -4-yl)methyl]imidazole, potassium salt} on angiotensin II (AII) 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 AII from its specific binding sites with high affinity (IC50 = 200 nmol/L) and antagonized the vasoconstrictive effect of AII in a dose-related manner with an ED50 of 170 nmol/L. These effects of DuP 753 were qualitatively similar to those of saralasin and the antagonist effect of DuP 753 on AII-induced renal vasoconstriction was fully overcome by excess AII. 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 1 μmol/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 angiotension II receptors in isolated perfused rat kidney and in cultured glomerular mesangial and renomedullary interstitial cells.

UR - http://www.scopus.com/inward/record.url?scp=0025760608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025760608&partnerID=8YFLogxK

M3 - Article

C2 - 1854456

AN - SCOPUS:0025760608

VL - 4

JO - Journal of clinical hypertension

JF - Journal of clinical hypertension

SN - 0895-7061

IS - 4 II SUPPL.

ER -