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

• J. Gregory Modrall

  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.

• Javid Sadjadi

  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.

• K. Bridget Brosnihan

  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.

• Patricia E. Gallagher

  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.

• Chun-hua Yu

  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.

• Gerald L. Kramer

  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.

• Kenneth E. Bernstein

  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.

• 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.

抄録

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 <0.02) and urinary volume was increased (7.25±0.86 versus 2.86±0.48 mL/d; P <0.001) in 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 <0.001). Intrarenal angiotensin I levels also declined by a comparable extent (73%) in the tis ACE −/− 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 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 <0.01). These studies suggest 2 potential mechanisms for the reduction of intrarenal angiotensin II in 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.

収録刊行物

• Hypertension

  Hypertension 43 (4), 849-853, 2004-04

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Internal Medicine

詳細情報

• CRID: 1360581244451359616
• NII論文ID: 30022677926
• DOI: 10.1161/01.hyp.0000121462.27393.f6
• ISSN: 15244563
• ISSN: 0194911X
• Web Site: https://www.ahajournals.org/doi/full/10.1161/01.HYP.0000121462.27393.f6
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