Vol. 284, Issue 6, H1969-H1977, June 2003
SPECIAL TOPICS
Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting-Enzyme Systems
Role of
bradykinin in angiotensin-converting enzyme knockout mice
Hong D.
Xiao,
Sebastien
Fuchs,
Justin M.
Cole,
Kevin M.
Disher,
Roy L.
Sutliff, and
Kenneth E.
Bernstein
Department of Pathology, Emory University, Atlanta, Georgia
30322
Angiotensin-converting enzyme (ACE) plays
a central role in the renin-angiotensin system. Whereas ACE is
responsible for the production of angiotensin II, it is also important
in the elimination of bradykinin. Constitutively, the biological
function of bradykinin is mediated through the bradykinin
B2 receptor. ACE knockout mice have a complicated phenotype
including very low blood pressure. To investigate the role of
bradykinin in the expression of the ACE knockout phenotype, we bred
B2 receptor knockout mice with ACE knockout mice, thus
generating a line of mice deficient in both the B2 receptor
and ACE. Surprisingly, these mice did not differ from ACE knockout mice
in blood pressure, urine concentrating ability, renal pathology, and
hematocrit. Thus abnormalities of bradykinin accumulation do not play
an important role in the ACE knockout phenotype. Rather, this phenotype
appears due to the defective production of angiotensin II.
blood pressure; urine osmolality; angiotensin II
