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.
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
Title and authors | Publication | Year |
---|---|---|
Targeting the degradation of angiotensin II with recombinant angiotensin-converting enzyme 2: prevention of angiotensin II-dependent hypertension
J Wysocki, M Ye, E Rodriguez, FR González-Pacheco, C Barrios, K Evora, M Schuster, H Loibner, KB Brosnihan, CM Ferrario, JM Penninger, D Batlle |
Hypertension | 2009 |
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
The sweeter side of ACE2: Physiological evidence for a role in diabetes
SM Bindom, E Lazartigues |
Molecular and Cellular Endocrinology | 2009 |
Does ACE2 contribute to the development of hypertension?
MC Chappell |
Hypertension research : official journal of the Japanese Society of Hypertension | 2009 |
Not just angiotensinases: new roles for the angiotensin-converting enzymes
DW Lambert, NE Clarke, AJ Turner |
Cellular and Molecular Life Sciences | 2009 |
The role of ACE2 in pulmonary diseases--relevance for the nephrologist
GY Oudit, Y Imai, K Kuba, JW Scholey, JM Penninger |
Nephrology Dialysis Transplantation | 2009 |
Angiotensin-(1-7), Angiotensin-Converting Enzyme 2, and New Components of the Renin Angiotensin System
Trask AJ, Varagic J, Ahmad S, Ferrario CM |
2009 |