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Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice
Susan B. Gurley, … , Howard A. Rockman, Thomas M. Coffman
Susan B. Gurley, … , Howard A. Rockman, Thomas M. Coffman
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2218-2225. https://doi.org/10.1172/JCI16980.
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Research Article Cardiology

Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice

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Abstract

The carboxypeptidase ACE2 is a homologue of angiotensin-converting enzyme (ACE). To clarify the physiological roles of ACE2, we generated mice with targeted disruption of the Ace2 gene. ACE2-deficient mice were viable, fertile, and lacked any gross structural abnormalities. We found normal cardiac dimensions and function in ACE2-deficient animals with mixed or inbred genetic backgrounds. On the C57BL/6 background, ACE2 deficiency was associated with a modest increase in blood pressure, whereas the absence of ACE2 had no effect on baseline blood pressures in 129/SvEv mice. After acute Ang II infusion, plasma concentrations of Ang II increased almost 3-fold higher in ACE2-deficient mice than in controls. In a model of Ang II–dependent hypertension, blood pressures were substantially higher in the ACE2-deficient mice than in WT. Severe hypertension in ACE2-deficient mice was associated with exaggerated accumulation of Ang II in the kidney, as determined by MALDI-TOF mass spectrometry. Although the absence of functional ACE2 causes enhanced susceptibility to Ang II–induced hypertension, we found no evidence for a role of ACE2 in the regulation of cardiac structure or function. Our data suggest that ACE2 is a functional component of the renin-angiotensin system, metabolizing Ang II and thereby contributing to regulation of blood pressure.

Authors

Susan B. Gurley, Alicia Allred, Thu H. Le, Robert Griffiths, Lan Mao, Nisha Philip, Timothy A. Haystead, Mary Donoghue, Roger E. Breitbart, Susan L. Acton, Howard A. Rockman, Thomas M. Coffman

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Figure 5

Measurement of renal angiotensin peptides using MALDI-TOF mass spectrometry.

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Measurement of renal angiotensin peptides using MALDI-TOF mass spectrome...
Representative spectrum for kidney extracts from a WT (A) and an ACE2-deficient mouse (B) after chronic infusion of Ang II. Ang I was added to both samples as an internal standard (IS). The level of Ang II is represented by the peak corresponding to the molecular weight at 1,046.44 m/z (mass-to-charge ratio) in kidney extracts from a WT mouse (A) and an ACE2-deficient mouse (B). Compared with kidneys from WT controls, Ang II was increased nearly 6-fold in kidneys from ACE2-deficient mice. *P = 0.0008.

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