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) 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 approximately 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.
Allan
D R
DR
Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Hui
K Y
KY
Coletti
C
C
Hollenberg
N K
NK
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000092502:Renin Inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D009842:Oligopeptides; D011480:Protease Inhibitors; D000092502:Renin Inhibitors; C027509:renin inhibitory peptide