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

J Clin Invest. 2006 Aug;116(8):2218-25. doi: 10.1172/JCI16980. Epub 2006 Jul 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / blood
  • Angiotensin II / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / genetics
  • Blood Pressure / physiology*
  • Crosses, Genetic
  • Female
  • Fertility
  • Heart / drug effects
  • Heart / physiology*
  • Infusions, Intravenous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptidyl-Dipeptidase A / deficiency*
  • Peptidyl-Dipeptidase A / genetics*
  • Reference Values

Substances

  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2