Renal and metabolic clearance of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) during angiotensin-converting enzyme inhibition in humans
Renal and metabolic clearance of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) during angiotensin-converting enzyme inhibition in humans
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DOI：
10.1161/01.hyp.33.3.879
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发表时间：
1999-03-01
期刊：
影响因子：
8.3
通讯作者：
Ménard, J
中科院分区：
文献类型：
--
作者：
Azizi, M;Ezan, E;Ménard, J
我们研究了血管紧张素转换酶（ACE）和肾小球滤过对血液调节肽N-乙酰-丝氨酰-赖氨酰-脯氨酸（AcSDKP）产生新的代谢平衡的贡献，AcSDKP在健康受试者的急性和慢性ACE抑制期间发生。我们还研究了慢性肾功能衰竭对长期ACE抑制剂（ACEI）治疗期间或不治疗时AcSDKP血浆浓度的影响。在健康受试者中，单次口服50 mg卡托普利（n = 32）和连续7天给予50 mg卡托普利BID（n = 10）分别导致42倍（范围：18 - 265倍）和34倍尿AcSDKP与肌酐的比值增加（范围，24倍至45倍），伴随4倍血浆AcSDKP水平增加4.8倍（范围，2 - 6.8倍）和4.8倍（范围，2.6 - 11.8倍）。血浆AcSDKP和体外ACE活性随时间的变化表明，在每个剂量的卡托普利之间，ACE间歇性再激活。慢性肾衰竭受试者（肌酐清除率
We investigated the contributions of angiotensin-converting enzyme (ACE) and glomerular filtration to creating the new metabolic balance of the hemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) that occurs during acute and chronic ACE inhibition in healthy subjects. We also studied the effect of chronic renal failure on the plasma concentration of AcSDKP during long-term ACE inhibitor (ACEI) treatment or in its absence. In healthy subjects, a single oral dose of 50 mg captopril (n=32) and a 7-day administration of 50 mg captopril BID (n=10) resulted in a respective 42-fold (range, 18- to 265-fold) and 34-fold (range, 24-fold to 45-fold) increase in the ratio of urinary AcSDKP to creatinine accompanied by a 4-fold (range, 2- to 6.8-fold) and 4.8-fold (range, 2.6- to 11.8-fold) increase in plasma AcSDKP levels. Changes in plasma AcSDKP and in vitro ACE activity over time showed an intermittent reactivation of ACE between each captopril dose. In subjects with chronic renal failure (creatinine clearance