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 produces an induction of plasma angiotensin converting enzyme. Induction of angiotensin converting enzyme in tissues during prolonged treatment with an angiotensin converting enzyme inhibitor is less well documented. 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. As an increase in activity could be masked by the inhibition due to the presence of ramiprilat which is the active form of ramipril, we eliminated the ramiprilat present in renal cortex homogenates with EGTA during brush border preparation. The 1-h treatment with ramipril induced a dose-dependent inhibition of plasma and renal cortex angiotensin converting enzyme activity. The 1-week treatment with ramipril produced an increase in plasma angiotensin converting enzyme activity, whereas renal cortex angiotensin converting enzyme activity decreased. The decrease in angiotensin converting enzyme activity persisted in the brush border membrane after elimination of residual ramiprilat with EGTA. Our results show that prolonged ramipril treatment produces opposite responses in plasma and renal cortex angiotensin converting enzyme activity, suggesting that plasma and epithelial angiotensin converting enzymes are subject to specific local regulatory factors.
Michel
B
B
Institut de Pharmacologie, URA DO589 CNRS, Université Louis Pasteur, Strasbourg, France.
Stephan
D
D
Grima
M
M
Barthelmebs
M
M
Imbs
J L
JL
D000818:Animals; D001665:Binding Sites; D002614:Chelating Agents; D004533:Egtazic Acid; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008871:Microvilli / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D017257:Ramipril / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013997:Time Factors; D015032:Zinc
D002614:Chelating Agents; D004533:Egtazic Acid; D007703:Peptidyl-Dipeptidase A; D015032:Zinc; D017257:Ramipril