Vol. 283, Issue 2, 661-665, 1997

Renin vs. Angiotensin-Converting Enzyme Inhibition in the Rat: Consequences for Plasma and Renal Tissue Angiotensin¹

D. R. Allan², K. Y. Hui³, C. Coletti and N. K. Hollenberg

From the Departments of Medicine and Radiology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA.

To compare the effects of a potent rat renin inhibitor peptide (RIP) and angiotensin-converting enzyme (ACE) inhibitor on the intrarenal and plasma renin-angiotensin systems, anesthetized Sprague-Dawley rats were treated with an infusion of vehicle, ramipril or graded doses of the rat RIP (acetyl-His-Pro-Phe-Val-statine-Leu-he-NH₂) for 30 min. Kidney and plasma samples were processed rapidly, and angiotensin peptides were separated by high-pressure liquid chromatography before measurement by a double-antibody radioimmunoassay. Blood pressure fell identically, by ~15 mm Hg, after either the RIP or ACE inhibitor. Plasma 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 highest RIP dose used. Control renal tissue Ang II was 183 ± 18 fmol/g, fell 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 sharp drop in Ang I conversion after ramipril in plasma and tissue. RIP did not influence conversion rate in plasma but was associated with an unanticipated fall in Ang I conversion in renal tissue, perhaps reflecting local aspartyl protease inhibition, which contributes to normal Ang II formation. Also unanticipated was a rise in tissue Ang I concentration during RIP administration. Renin inhibition is more effective than ACE inhibition in blocking systemic Ang II formation, supporting studies suggesting that quantitatively important non-ACE-dependent pathways participate in Ang II formation.