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(Circulation Research. 2002;90:87.)
© 2002 American Heart Association, Inc.

Integrative Physiology

Mice Lacking Endothelial Angiotensin-Converting Enzyme Have a Normal Blood Pressure

Justin Cole, Du Le Quach, Karthik Sundaram, Pierre Corvol, Mario R. Capecchi, Kenneth E. Bernstein

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

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

To test the hypothesis that local vascular production of angiotensin II is necessary for the normal regulation of blood pressure, we engineered a new line of genetically altered mice that lack endothelial angiotensin-converting enzyme (ACE). This was accomplished using a novel strategy of targeted homologous recombination to separate the transcriptional control of somatic ACE from its endogenous promoter and to substitute control to the albumin promoter. These new mice, termed ACE.3, do not produce ACE within the lung, the aorta, or any vascular structure. ACE activity within the kidney is only about 14% that of wild-type mice and is limited to tubular epithelium. In contrast, hepatic ACE expression in ACE.3 mice is about 87-fold that of wild-type. The blood pressure, plasma angiotensin II levels, response to ACE inhibitors, and renal function of ACE.3^-/- mice are indistinguishable from littermate wild-type mice. These data show that, under basal conditions, the normal regulation of blood pressure and renal function is possible in a mouse devoid of endothelial ACE.

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

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