Sequential Changes of Angiotensin-Converting Enzyme Gene Expression in Lung and Myocardium after Myocardial Infarction in Rat:Different Patterns of Expression and Regulation between Circulating and Local System

Youn, Tae Jin; Kim, Hyo Soo; Kim, Duk Kyung; Kim, Cheol Ho; Lee, Myoung Mook

Abstract

BACKGROUND: We evaluated 1) the sequential changes of angiotensin-converting enzyme (ACE) mRNA expression in lung (main site for circulating ACE synthesis) and left ventricle, and 2) whether such expression is modified by ACE inhibitor or angiotensin II receptor blocker treatment after acute myocardial infarction (MI) in rats.
METHODS
Placebo, captopril (2 g/liter drinking water) or TCV-116 (10 mg/kg/day gavage) was administered 3 days before left coronary occlusion and continued for 6 weeks. At 1, 3 and 6 weeks after operation, hemodynamic measurement was performed and pulmonary and myocardial ACE mRNA expression was analyzed by quantitative RT-PCR using rcRNA as an internal standard.
RESULTS
Mean BP and LVEDP increased in untreated rats compared with captopril- and TCV-116-treated rats (post-MI 6week, p<0.05). Pulmonary ACE mRNA increased in acute phase (post-MI 1 week, max. 1.4 fold, p<0.05 vs. pre-MI) and returned to pre-MI value thereafter. In contrast, cardiac ACE mRNA expression showed slightly decreasing tendency in acute phase, and was increased up to 1.6 fold in chronic phase after MI (post-MI 3 and 6weeks, p<0.05 vs. pre-MI). No changes in pulmonary ACE gene expression were found with RAS blockade. However, in acute phase after MI, cardiac ACE mRNA increased with both captopril and TCV-116 treatment (post-MI 24hour and 1week, max. 2 fold, p<0.05 vs. untreated group).
CONCLUSION
1) In contrast to the pulmonary ACE mRNA that is activated in acute phase, the cardiac ACE mRNA is activated in chronic phase after MI. 2) RAS blockade does not affect the change of pulmonary ACE expression, but modulate the change of cardiac ACE expression after MI.