DeForrest J M, Waldron T L, Powell J R, Floyd D M, Sundeen J E
J Cardiovasc Pharmacol. 1987 Feb;9(2):154-9. doi: 10.1097/00005344-198702000-00005.
SQ 27,786 and SQ 28,853 were designed to possess both angiotensin converting enzyme (ACE) inhibitory and diuretic properties. Both compounds were given to conscious male Sprague-Dawley rats and mongrel female dogs to determine ACE inhibitory and diuretic activities. All animals had previously been equipped with indwelling arterial and venous catheters. Both compounds resulted in dose-related inhibition of an angiotensin I pressor response in rats after i.v. administration. The maximum response and duration of effect of both compounds were similar to that seen with equimolar doses of captopril. Oral doses of SQ 28,853 (50.0 mumol/kg) and SQ 27,786 (15.0 mumol/kg) resulted in 15 and 64% inhibition of ACE, respectively. In conscious normotensive dogs, both compounds (2.0 mg/kg, i.v.) resulted in complete inhibition of ACE. Urine volume was increased by 153 and 667% after SQ 27,786 and SQ 28,853, respectively. Similarly, sodium excretion was increased by 336% after SQ 27,786 and by 650% after SQ 28,853. SQ 27,786 and SQ 28,853 increased potassium excretion by 54 and 115%, respectively. No significant changes in blood pressure were observed with either compound in either species. These results demonstrate that both SQ 27,786 and SQ 28,853 are potent ACE inhibitors and diuretic agents in vivo.
SQ 27786和SQ 28853被设计成同时具有血管紧张素转换酶（ACE）抑制和利尿特性。将这两种化合物给予清醒的雄性斯普拉格-道利大鼠和杂种雌性犬，以测定ACE抑制和利尿活性。所有动物先前都已植入了动脉和静脉导管。两种化合物静脉注射后均导致大鼠体内血管紧张素I升压反应呈剂量依赖性抑制。两种化合物的最大反应和作用持续时间与等摩尔剂量的卡托普利相似。口服剂量的SQ 28853（50.0 μmol/kg）和SQ 27786（15.0 μmol/kg）分别导致ACE抑制15%和64%。在清醒的正常血压犬中，两种化合物（2.0 mg/kg，静脉注射）均导致ACE完全抑制。SQ 27786和SQ 28853给药后，尿量分别增加了153%和667%。同样，SQ 27786给药后钠排泄增加了336%，SQ 28853给药后增加了650%。SQ 27786和SQ 28853分别使钾排泄增加了54%和115%。两种化合物在两种动物中均未观察到血压有显著变化。这些结果表明，SQ 27786和SQ 28853在体内都是有效的ACE抑制剂和利尿剂。
