Effect of chronic angiotensin converting enzyme inhibition on angiotensin I and bradykinin metabolism in rats

摘要: We determined the effect of chronic administration angiotensin converting enzyme (ACE) inhibitor, enalapril, on in vivo pulmonary inactivation bradykinin (BK) and conversion I (Ang I). In addition we assessed whether ACE inhibition influenced activity prolylendopeptidase (PEP), which metabolizes Ang to generate angiotensin-(1-7) (Ang-[1-7]) inactivates BK. Male Wistar rats were treated orally with enalapril (10 mg/kg once a day) for 7 15 days (n = 20) 21 30 11). Vehicle-treated (7 days, n 11) used as controls. Pulmonary BK conscious enalapril- or vehicle-treated before after intravenous inhibitor enalaprilat (MK-422, 10 mg/kg). (%) was by comparing equipotent doses injected intraaortic routes, pressor II intravenously. PEP-like plasma lung homogenates fluorometrically using synthetic substrate Suc-Gly-Pro-MCA. control rats, averaged 97.6% ± 0.54%. Acute MK-422 reduced 42.0% 2.7%. However, chronically increased compared acute inhibition, averaging 58.8% 3.7% at 4.5% treatment. Intravenous enalapril-treated did not return level observed during inhibition. contrast, significantly from 46.7% 6.5% 0.9% 0.2% MK-422, this remained essentially unchanged 4.4 0.3 nmol MCA/min/mL 11.4 0.9 MCA/min/mg protein, respectively. After treatment there progressive increase both lung, 10.7 1.7 29.2 2.8 These data indicate that blockade induces alternative BK-inactivating mechanisms increases Ang-(1-7)-generating mechanisms.