大鼠心脏中的血管紧张素转换酶：其体外和体内抑制作用的研究。

Angiotensin converting enzyme in the rat heart: studies of its inhibition in vitro and ex vivo.

Fabris B, Jackson B, Cubela R, Mendelsohn F A, Johnston C I

University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.

Clin Exp Pharmacol Physiol. 1989 Apr;16(4):309-13. doi: 10.1111/j.1440-1681.1989.tb01563.x.

Abstract

The pharmacokinetics of angiotensin converting enzyme (ACE) inhibition in rat heart and lung was evaluated in vitro and ex vivo. 2. Radioinhibitor [125I]-351A binding displacement was used to assess the relative potency of six ACE-inhibitors (CI906, CGS14831, S9780, 351A, MK521, SQ27519) in rat heart and lung homogenates, and estimate equilibrium association constant (Ka). 3. Following oral administration of 0.3 mg/kg of Quinapril (CI928) specific binding of [125I]-351A to ACE was measured in rat heart. 4. Ka for binding to ACE of each inhibitor was significantly higher in right and left atrium than in lung (P less than 0.05) or the right and left ventricle (P less than 0.005). These differences did not affect the degree or time course of inhibition in vivo in the rat myocardial ACE following Quinapril treatment. 5. Rank order of potency of the ACE inhibitors tested was CI906 = CGS14831 greater than S9780 greater than 351A greater than MK521 greater than SQ27519

摘要

在体外和离体条件下评估了血管紧张素转换酶（ACE）抑制剂在大鼠心脏和肺中的药代动力学。2. 采用放射性抑制剂[125I]-351A结合置换法，评估了六种ACE抑制剂（CI906、CGS14831、S9780、351A、MK521、SQ27519）在大鼠心脏和肺匀浆中的相对效力，并估算平衡缔合常数（Ka）。3. 口服0.3mg/kg喹那普利（CI928）后，测定了[125I]-351A与大鼠心脏中ACE的特异性结合。4. 每种抑制剂与ACE结合的Ka在左右心房中显著高于肺（P<0.05）或左右心室（P<0.005）。这些差异并不影响喹那普利治疗后大鼠心肌ACE体内抑制的程度或时间进程。5. 所测试的ACE抑制剂的效力排序为CI906 = CGS14831>S9780>351A>MK521>SQ27519