title: Mice lacking endothelial angiotensin-converting enzyme have a normal blood pressure.
abstract: 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.
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Cole
authors.forename: Du Le
authors.initials: DL
authors.lastname: Quach
authors.forename: Karthik
authors.initials: K
authors.lastname: Sundaram
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.forename: Mario R
authors.initials: MR
authors.lastname: Capecchi
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D005838:Genotype; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*
chemical_list: D007703:Peptidyl-Dipeptidase A