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(Hypertension. 2004;43:849.)
© 2004 American Heart Association, Inc.

Scientific Contributions

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

J. Gregory Modrall; Javid Sadjadi; K. Bridget Brosnihan; Patricia E. Gallagher; Chun-hua Yu; Gerald L. Kramer; Kenneth E. Bernstein; Mark C. Chappell

From the Department of Surgery (J.G.M., J.S., C.Y., G.L.K.), University of Texas Southwestern Medical Center, Dallas; Hypertension and Vascular Disease Center (M.C.C., K.B.B., P.E.G.), Wake Forest University School of Medicine, Winston-Salem, NC; and Department of Pathology (K.E.B.), Emory University School of Medicine, Atlanta, Ga.

Correspondence to Dr J. Gregory Modrall, Division of Vascular Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9157. E-mail greg.modrall{at}utsouthwestern.edu

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 (tisACE^-/-) mouse model. Systolic blood pressure was significantly lower (64.6±3.6 versus 81.4±4.5 mm Hg; P<0.02) and urinary volume was increased (7.25±0.86 versus 2.86±0.48 mL/d; P<0.001) in tisACE^-/- mice compared with wild-type mice. Intrarenal angiotensin II was 80% lower in tisACE^-/- mice compared with wild-type mice (5.17±0.60 versus 25.5±2.4 fmol/mg protein; P<0.001). Intrarenal angiotensin I levels also declined by a comparable extent (73%) in the tisACE^-/- mice (P<0.01). Intrarenal angiotensin-(1–7) concentrations were similar between the strains, but the ratio of intrarenal angiotensin-(1–7) to angiotensin II and angiotensin I in tisACE^-/- 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 tisACE^-/- mice (P<0.01). These studies suggest 2 potential mechanisms for the reduction of intrarenal angiotensin II in tisACE^-/- 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 tisACE^-/- mice, particularly in the context of depleted angiotensin II in the kidney.

Key Words: angiotensin II • angiotensin I • renin-angiotensin system • mice

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