The role of locally expressed angiotensin converting enzyme in cardiac remodeling after myocardial infarction in mice

Objective: Angiotensin 11, generated from angiotensin I by angiotensin converting enzyme (ACE), induces multiple effects including vasoconstriction, positive cardiac inotropy, hypertrophy of cardiomyocytes and proliferation of fibroblasts. ACE exists both in a tissue-bound (t-ACE) and a soluble form. The functional importance of locally produced angiotensin 11 is still unclear. In the present study, mice lacking tissue-bound angiotensin converting enzyme (t-ACE -/-) were used to investigate the importance of t-ACE during cardiac remodeling after myocardial infarction. Methods: Mice were subjected to coronary artery occlusion or sham surgery. At 14 days after MI, stroke volume (SV) was determined with an electromagnetic flow probe around the ascending aorta. Mean arterial pressure (MAP) was measured through a carmula in the abdominal aorta. Both parameters were determined at rest and after a volume loading of 2.5 ml warm (37 degreesC) Ringer's solution in 60 s. Hearts were dissected and formalin-fixed to measure infarct size, cardiac dimensions and collagen concentration. Tissue levels of angiotensin I and 11 were determined in hearts and kidneys. Results: At rest, under pentobarbital anaesthesia, t-ACE -/- mice (n=12) exhibited a significantly lower MAP (26+/-3 vs. 45+/-3 mmHg) than t-ACE +/+ (n=11). SV was similar in both strains. Maximal SV was significantly reduced after MI. Furthermore, infarcted t-ACE -/- (n=6) exhibited a significantly lower maximal SV compared to infarcted t-ACE +/+ mice (n=5; 20.4+/-1.5 vs. 29.6+/-2.3 RI). Structural cardiac parameters as well as cardiac and renal angiotensin 11 levels in t-ACE -/- and t-ACE +/+ were comparable. Conclusions: These results suggest that the structural adaptations of the heart that follow MI are independent of t-ACE. However, the presence of t-ACE is necessary for maintenance of cardiac function. (C) 2002 Elsevier Science B.V. All rights reserved.