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.
N1 - Funding Information:
This research was supported by National Institutes of Health grant DK 14241. Dr. Fontoura is supported by a fellowship from Coorde-naçao de Aperfeiçoamento de Pessoal de Nivel Superior, Brazil.
PY - 1991/4
Y1 - 1991/4
N2 - 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.
AB - 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.
KW - Angiotensin II binding
KW - Glomerular mesangial cells
KW - Isolated perfused rat kidney
KW - Renal vasoconstriction
KW - Renomedullary interstitial cells
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U2 - 10.1093/ajh/4.4.303S
DO - 10.1093/ajh/4.4.303S
M3 - Article
C2 - 1854456
AN - SCOPUS:0025760608
SN - 0895-7061
VL - 4
SP - 303s-308s
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 4
ER -