Mice expressing ACE only in the heart show that increased cardiac angiotensin II is not associated with cardiac hypertrophy

Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H659-67. doi: 10.1152/ajpheart.01147.2007. Epub 2007 Nov 21.

Abstract

In the heart, angiotensin II has been suggested to regulate cardiac remodeling and promote cardiac hypertrophy. To examine this, we studied compound heterozygous mice, called angiotensin-converting enzyme (ACE) 1/8, in which one ACE allele is null, whereas the other ACE allele (the 8 allele) targets expression to the heart. In this model, cardiac ACE levels are about 15 times those of wild-type mice, and ACE expression is reduced or eliminated in other tissues. ACE 1/8 mice have 58% the cardiac ACE of a previous model, called ACE 8/8, but both ACE 1/8 and ACE 8/8 mice have ventricular angiotensin II levels about twofold those of wild-type controls. Despite equivalent levels of cardiac angiotensin II, ACE 1/8 mice do not develop the marked atrial enlargement or the conduction defects previously reported in the ACE 8/8 mice. Six-month-old ACE 1/8 mice have normal cardiac function, as determined by echocardiography and left ventricular catheterization, despite the elevated levels of angiotensin II. ACE 1/8 mice also have normal levels of connexin 43. Both wild-type and ACE 1/8 mice develop similar degrees of cardiac hypertrophy after aortic banding. These data suggest that a moderate increase of local angiotensin II production in the heart does not produce cardiac dysfunction, at least under basal conditions, and that, in response to aortic banding, cardiac hypertrophy is not augmented by a twofold increase of cardiac angiotensin II.

Publication types

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

MeSH terms

  • Alleles
  • Angiotensin I / blood
  • Angiotensin I / metabolism
  • Angiotensin II / biosynthesis*
  • Angiotensin II / physiology*
  • Angiotensinogen / genetics
  • Animals
  • Aorta, Abdominal / physiology
  • Blood Pressure / physiology
  • Blotting, Western
  • Cardiac Catheterization
  • Cardiomegaly / etiology*
  • Cardiomegaly / metabolism*
  • Connexin 43 / metabolism
  • DNA / genetics
  • Electrocardiography
  • Heart / physiology
  • Kidney / physiology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Myocardium / enzymology*
  • Osmolar Concentration
  • Peptidyl-Dipeptidase A / biosynthesis*
  • Peptidyl-Dipeptidase A / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Distribution
  • Ventricular Function, Left

Substances

  • Connexin 43
  • Angiotensinogen
  • Angiotensin II
  • DNA
  • Angiotensin I
  • Peptidyl-Dipeptidase A