Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice

Gurley, S.B. et al. (2006) Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. Journal of Clinical Investigation, 116(8), pp. 2218-2225. (doi: 10.1172/JCI16980)

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Abstract

The carboxypeptidase ACE2 is a homologue of angiotensin-converting enzyme (ACE). To clarify the physiological roles of ACE2, we generated mice with targeted disruption of the Ace2 gene. ACE2-deficient mice were viable, fertile, and lacked any gross structural abnormalities. We found normal cardiac dimensions and function in ACE2-deficient animals with mixed or inbred genetic backgrounds. On the C57BL/6 background, ACE2 deficiency was associated with a modest increase in blood pressure, whereas the absence of ACE2 had no effect on baseline blood pressures in 129/SvEv mice. After acute Ang II infusion, plasma concentrations of Ang II increased almost 3-fold higher in ACE2-deficient mice than in controls. In a model of Ang II-dependent hypertension, blood pressures were substantially higher in the ACE2-deficient mice than in WT. Severe hypertension in ACE2-deficient mice was associated with exaggerated accumulation of Ang II in the kidney, as determined by MALDI-TOF mass spectrometry. Although the absence of functional ACE2 causes enhanced susceptibility to Ang II-induced hypertension, we found no evidence for a role of ACE2 in the regulation of cardiac structure or function. Our data suggest that ACE2 is a functional component of the renin-angiotensin system, metabolizing Ang II and thereby contributing to regulation of blood pressure.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Philip, Dr Nisha
Authors: Gurley, S.B., Allred, A., Le Thu, H., Griffiths, R., Mao, L., Philip, N., Haystead, T.A., Donoghue, M., Breitbart, R.E., Acton, S.L., Rockman, H.A., and Coffman, T.M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Clinical Investigation
Publisher:Americal Society for Clinical Investigation
ISSN:0021-9738
ISSN (Online):1558-8238

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