Hearts of normotensive
angiotensin II type 2 receptor (AT2)-deficient mice do not develop
fibrosis after
angiotensin II-induced chronic
hypertension. Thus, the goal of our study was to clarify whether AT2 knockouts (KOs) are also characterized by altered left ventricular (LV) function and modified remodeling of the extracellular matrix (ECM) after induction of
myocardial infarction (MI). MI was induced in 5-mo-old female AT2-deficient mice and controls by occlusion of the left coronary artery. Time-matched
sham-operated animals served as controls. After 48 h, the first sets of mice were hemodynamically characterized using a pressure-tip
catheter (n = 8/group). We also obtained pressure volume loops using a microconductance
catheter in additional sets of animals 3 wk after induction of MI (n = 7/group). Finally, the
collagen index was illustrated by Sirius red staining and quantified by digital analysis. Whereas the LV function of
sham-operated animals did not differ between both genotypes, the
collagen index was 44% lower in KO animals. Forty-eight hours and 3 wk post-MI, systolic and diastolic LV function were impaired in both AT2-deficient and wild-type (WT) animals to the same extent by approx 45%. No differences were found between the two genotypes with respect to LV
hypertrophy and the
fibrosis index in the infarcted and noninfarcted areas 3 wk post-MI. While AT2-KO mice had less cardiac
collagen content under basal conditions, the receptor deficiency had no significant influence on LV function at the two investigated time points after induction of MI or on the remodeling of ECM at the latter time point. Thus,
hypertension-induced
fibrosis is probably triggered by other control mechanisms than
fibrosis induced by MI.