DuP 753 is a potent nonpeptide antagonist of angiotensin II receptors in isolated perfused rat kidney and cultured renal cells.
DuP 753 is a potent nonpeptide antagonist of angiotensin II receptors in isolated perfused rat kidney and cultured renal cells.
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DuP 753 是离体灌注大鼠肾和培养肾细胞中血管紧张素 II 受体的有效非肽拮抗剂。
DOI：
10.1093/ajh/4.4.303s
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发表时间：
1991
影响因子：
3.2
通讯作者：
Maack,T
中科院分区：
文献类型：
--
作者：
Fontoura,BM;Nussenzveig,DR;Timmermans,PB;Maack,T
In the present study we investigated the antagonist action of DuP 753 {2 - n - butyl - 4 - chloro - 5 - hydroxymethyl - 1 - [2’ - (1H - tetrazol - 5 - y1)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 ED50of 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 1μmol/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 II receptors in isolated perfused rat kidney and in cultured glomerular mesangial and renomedullary interstitial cells. Am J Hypertens 1991;4:303S-308S
