DIETARY NA AND ACE INHIBITION EFFECTS ON RENAL TISSUE ANGIOTENSIN-I AND ANGIOTENSIN-II AND ACE ACTIVITY IN RATS

This study was designed to improve and validate methods for the accurate and consistent quantitation of angiotensin (ANG) I and II levels in rat kidney and to determine the effects on renal ANG I and II of changes in dietary sodium intake and ANG-converting enzyme (ACE) inhibition. Kidneys from pentobarbital-anesthetized rats were rapidly removed and homogenized in methanol before extraction and purification of ANG peptides by solid-phase extraction and high-performance liquid chromatography (HPLC). Recoveries of I-125-ANG I and II were > 80%. Reversed-phase HPLC of the partially purified methanol extract showed that > 75% of the ANG-I and > 82% of the ANG II-like immunoreactivity coeluted with ANG I and II, respectively. Dietary sodium deprivation (0.003 meq/g) and excess (1.34 meq/g) for 7 days significantly (P < 0.01) increased and decreased renal ANG I (296 +/- 30 and 82.6 +/- 15.8 vs. 161 +/- 18 fmol/g) and ANG II (216 +/- 16 and 45.6 +/- 11.8 vs. 98 +/- 16 fmol/g) contents, respectively. Plasma ANG I and II levels showed similar changes. ACE activity was significantly upregulated by sodium deprivation in both kidney (44% increase) and plasma (30% increase). In rats fed normal chow, infusion of enalaprilat for 1 h abolished plasma ACE activity but decreased renal ACE activity by only 58%. ACE inhibition increased renal and plasma ANG I levels 2.8- and 12-fold, respectively, and decreased renal and plasma ANG II levels 75-78%. These data indicate that renal ANG I and II contents are similar and are altered concomitantly by variations in dietary sodium but are markedly dissociated during ACE inhibition. Furthermore, acute ACE inhibition does not abolish renal ACE activity, suggesting continued local ANG II generation.