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  • Title: Acute and chronic effects of perindopril on tissue angiotensin converting enzyme activity.
    Author: Mendelsohn FA, Pupic V, Jackson B, Cubela R, Johnston CI.
    Journal: Am J Hypertens; 1991 Mar; 4(3 Pt 2):220S-225S. PubMed ID: 1645981.
    Abstract:
    The pattern of inhibition of tissue angiotensin converting enzyme (ACE) was studied in rats after acute and chronic (14 days) oral administration of perindopril. Free and total tissue ACE were measured by quantitative in vitro autoradiography using [125I]-351A as a radioligand and compared with plasma ACE and pressor responses to angiotensin I. Following oral perindopril, plasma perindoprilic acid and the pattern of inhibition of plasma ACE activity were maximal at 1 to 2 h, but recovered over 24 h. However, inhibition of the pressor response to angiotensin I was more prolonged, being 95% at 4 h, but had not fully recovered by 24 h. Acutely, ACE was markedly inhibited in renal proximal tubules, lung parenchyma, and aortic wall. At 24 h, ACE in these tissues had only partially recovered. Angiotensin converting enzyme in vascular endothelium of other organs showed a similar pattern of inhibition. In contrast, ACE in testicular seminiferous tubules was unaffected by perindopril. After chronic (14 days) administration of perindopril, total plasma ACE increased 3-fold, of which 49% was occupied by the inhibitor. Total tissue ACE in kidney and aorta did not change, and the pattern of inhibition observed acutely was maintained during chronic treatment. These results demonstrate a prolonged effect of ACE inhibitors on tissue ACE that may better explain the time course of these drugs than the changes in plasma ACE or plasma levels of the drugs.
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