Published Online
on December 30, 2002

A more recent version of this article appeared on February 1, 2003

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Submitted on August 15, 2002
Revised on September 5, 2002

Mice Lacking Endothelial ACE

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

^* To whom correspondence should be addressed. E-mail: kbernst{at}emory.edu.

Abstract—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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