EFFECTS OF ONE-HOUR AND ONE-WEEK TREATMENT WITH RAMIPRIL ON PLASMA AND RENAL BRUSH-BORDER ANGIOTENSIN-CONVERTING ENZYME IN THE RAT

Prolonged treatment with an angiotensin converting enzyme inhibitor pr oduces an induction of plasma angiotensin converting enzyme. Induction of angiotensin converting enzyme in tissues during prolonged treatmen t with an angiotensin converting enzyme inhibitor is less well documen ted. We compared the effects of 1 h and 1 week treatment with ramipril (0.1, 0.3, 1 mg/kg) on angiotensin converting enzyme activity in the plasma, renal cortex and renal brush border membrane of Wistar rats. A s an increase in activity could be masked by the inhibition due to the presence of ramiprilat which is the active form of ramipril, we elimi nated the ramiprilat present in renal cortex homogenates with EGTA dur ing brush border preparation. The 1-h treatment with ramipril induced a dose-dependent inhibition of plasma and renal cortex angiotensin con verting enzyme activity. The 1-week treatment with ramipril produced a n increase in plasma angiotensin converting enzyme activity, whereas r enal cortex angiotensin converting enzyme activity decreased. The decr ease in angiotensin converting enzyme activity persisted in the brush border membrane after elimination of residual ramiprilat with EGTA. Ou r results show that prolonged ramipril treatment produces opposite res ponses in plasma and renal cortex angiotensin converting enzyme activi ty, suggesting that plasma and epithelial angiotensin converting enzym es arc subject to specific local regulatory factors.