Depletion of Tissue Angiotensin-Converting Enzyme Differentially Influences the Intrarenal and Urinary Expression of Angiotensin Peptides

Abstract

The relative contribution of circulating versus tissue renin-angiotensin systems to the tissue expression of angiotensin peptides in the kidney remains unresolved. To address this issue, intrarenal and urinary levels of the peptide products of the renin-angiotensin system were assessed in a tissue angiotensin-converting enzyme knockout ( tis ACE ^−/− ) mouse model. Systolic blood pressure was significantly lower (64.6±3.6 versus 81.4±4.5 mm Hg; P P tis ACE ^−/− mice compared with wild-type mice. Intrarenal angiotensin II was 80% lower in tis ACE ^−/− mice compared with wild-type mice (5.17±0.60 versus 25.5±2.4 fmol/mg protein; P tis ACE ^−/− mice ( P tis ACE ^−/− mice increased 470% and 355%, respectively, compared with wild-type mice. Urinary excretion of angiotensin II and angiotensin-(1–7) were not different, but the excretion of angiotensin I increased 270% in tis ACE ^−/− mice ( P tis ACE ^−/− mice: (1) an attenuated capacity to form angiotensin II by renal angiotensin-converting enzyme and (2) significant depletion of its direct precursor angiotensin I in renal tissue. Sustained intrarenal levels of angiotensin-(1–7) may contribute to chronic hypotension and polyuria in tis ACE ^−/− mice, particularly in the context of depleted angiotensin II in the kidney.