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Hypertension. 2004 Apr;43(4):849-53. Epub 2004 Feb 23.

Depletion of tissue angiotensin-converting enzyme differentially influences the intrarenal and urinary expression of angiotensin peptides.

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1
Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9157, USA. greg.modrall@utsouthwestern.edu

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 (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.

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