Wong P C, Hart S D, Duncia J V, Timmermans P B
Du Pont Merck Pharmaceutical Company, Wilmington, DE 19880-0400.
Eur J Pharmacol. 1991 Sep 24;202(3):323-30. doi: 10.1016/0014-2999(91)90274-t.
DuP 753 (or EXP3174) and PD123177 are nonpeptide angiotensin (AII)-specific ligands, which show high affinities for two AII receptor subtypes, i.e. AT1 and AT2 sites, respectively. In furosemide-treated conscious dogs with high renin, DuP 753 and EXP3714, but not PD123177, were as effective as captopril in lowering blood pressure. Both DuP 753 and EXP3174 exhibited selective vascular antagonism of AII. In conscious dogs with normal renin, DuP 753, but not captopril or EXP3174, caused a dose-dependent but transient decrease in blood pressure. In anesthetized dogs, DuP 753 and captopril caused similar renal vasodilatation and natriuresis. The renal hemodynamic effects of DuP 753 and captopril were more pronounced in dogs with sodium depletion. These results suggest that the AT1 receptor mediates the pressor and renal effects of AII in dogs. The acute transient hypotensive effect of DuP 753 in normal-renin conscious dogs is probably unrelated to AII antagonism.
杜普753（或EXP3174）和PD123177是非肽类血管紧张素（AII）特异性配体，它们分别对两种AII受体亚型，即AT1和AT2位点，表现出高亲和力。在速尿治疗的高肾素清醒犬中，杜普753和EXP3714，而非PD123177，在降低血压方面与卡托普利效果相当。杜普753和EXP3174均表现出对AII的选择性血管拮抗作用。在肾素正常的清醒犬中，杜普753，而非卡托普利或EXP3174，引起剂量依赖性但短暂的血压下降。在麻醉犬中，杜普753和卡托普利引起相似的肾血管舒张和利钠作用。杜普753和卡托普利的肾血流动力学效应在缺钠犬中更为明显。这些结果表明，AT1受体介导了犬中AII的升压和肾效应。杜普753在肾素正常的清醒犬中的急性短暂降压作用可能与AII拮抗作用无关。
