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(Hypertension. 2003;41:313.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Mice Lacking Endothelial ACE

Normal Blood Pressure With Elevated Angiotensin II

Justin M. Cole; Nata Khokhlova; Roy L. Sutliff; Jonathan W. Adams; Kevin M. Disher; Hui Zhao; Mario R. Capecchi; Pierre Corvol; Kenneth E. Bernstein

From the Department of Pathology, Emory University (J.M.C., N.K., R.L.S., J.W.A., K.M.D., H.Z., K.E.B.), Atlanta, Ga; Howard Hughes Medical Institute, Eccles Institute of Human Genetics, University of Utah (M.R.C.), Salt Lake City; and Institut National de la Santé et de la Recherche Medicale Unit 36, College de France (P.C.), Paris.

Correspondence to Ken Bernstein, MD, Room 7107A WMB, Department of Pathology, Emory University, Atlanta, GA 30322. E-mail kbernst{at}emory.edu

Recently, the concept of local renin-angiotensin systems (RAS) capable of generating angiotensin II apart from the circulation has received considerable attention. To investigate this, we generated ACE 1/3 mice in which one allele of ACE is null and the second allele was engineered to express ACE on the surface of hepatocytes. ACE 1/3 mice express no endothelial ACE and lack ACE within the lungs. Their kidneys contain <7.8% the enzyme levels present in control mice. Plasma conversion of angiotensin I to angiotensin II was 43.3% normal. The baseline blood pressure and renal function of the ACE 1/3 mice were normal, probably as a function of a marked increase of both plasma angiotensin I and angiotensin II. When exposed to 2 weeks of a salt-free diet (a stress diet stimulating the RAS), blood pressure in ACE 1/3 mice decreased to 92.3±2.0 mm Hg, a level significantly lower than that of wild-type control mice. The ACE 1/3 mice demonstrate the plasticity of the RAS and show that significant compensation is required to maintain normal, basal blood pressure in a mouse with an impaired local vascular and renal RAS.

Key Words: mice, knockout • angiotensin-converting enzyme • angiotensin II • endothelium • blood pressure

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