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Am J Physiol Heart Circ Physiol 284: H1969-H1977, 2003. First published March 13, 2003; doi:10.1152/ajpheart.00010.2003
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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


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