Mice lacking endothelial ACE: normal blood pressure with elevated angiotensin II.
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.
Cole
Justin M
JM
Department of Pathology, Emory University, Atlanta, GA 30322, USA.
Khokhlova
Nata
N
Sutliff
Roy L
RL
Adams
Jonathan W
JW
Disher
Kevin M
KM
Zhao
Hui
H
Capecchi
Mario R
MR
Corvol
Pierre
P
Bernstein
Kenneth E
KE
D000803:Angiotensin I / Q000097:blood / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D010953:Plasma Volume / Q000187:drug effects; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage
D012982:Sodium, Dietary; D000804:Angiotensin II; D000803:Angiotensin I; D012964:Sodium; D007703:Peptidyl-Dipeptidase A