RENIN VS. ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN THE RAT - CONSEQUENCES FOR PLASMA AND RENAL TISSUE ANGIOTENSIN

To compare the effects of a potent rat renin inhibitor peptide (RIP) a nd angiotensin-converting enzyme (ACE) inhibitor on the intrarenal and plasma renin-angiotensin systems, anesthetized Sprague-Dawley rats we re treated with an infusion of vehicle, ramipril or graded doses of th e rat RIP (acetyl-His-Pro-Phe-Val-statine-Leu-he-NH2) for 30 min. Kidn ey and plasma samples were processed rapidly, and angiotensin peptides were separated by high-pressure liquid chromatography before measurem ent by a double-antibody radioimmunoassay. Blood pressure fell identic ally, by similar to 15 mm Hg, after either the RIP or ACE inhibitor, P lasma Ang II was 83 +/- 20 fmol/ml in vehicle-treated rats and fell to 28 +/- 3 fmol/ml with ramipril (10 mg/kg), the dose-response zenith. Plasma Ang II was significantly lower, 9 +/- 2 fmol/ml, with the highe st RIP dose used. Control renal tissue Ang II was 183 +/- 18 fmol/g, f ell with ramipril to 56 +/- 6 and then fell to a similar level (47 +/- 10 fmol/g) after RIP. Ang I/Ang II ratios indicated the expected shar p drop in Ang I conversion after ramipril in plasma and tissue. RIP di d not influence conversion rate in plasma but was associated with an u nanticipated fall in Ang I conversion in renal tissue, perhaps reflect ing local aspartyl protease inhibition, which contributes to normal An g II formation. Also unanticipated was a rise in tissue Ang I concentr ation during RIP administration. Renin inhibition is more effective th an ACE inhibition in blocking systemic Ang II formation, supporting st udies suggesting that quantitatively important non-ACE-dependent pathw ays participate in Ang II formation.