Increased angiotensin-converting enzyme activity in the left ventricle after infarction

Abstract

An increase in angiotensin-converting enzyme (ACE) activity has been observed in the heart after myocardial infarction (MI). Since most studies have been conducted in chronically infarcted individuals exhibiting variable degrees of heart failure, the present study was designed to determine ACE activity in an earlier phase of MI, before heart failure development. MI was produced in 3-month old male Wistar rats by ligation of the anterior branches of the left coronary artery, control rats underwent sham surgery and the animals were studied 7 or 15 days later. Hemodynamic data obtained for the anesthetized animals showed normal values of arterial blood pressure and of end-diastolic pressure in the right and left ventricular cavities of MI rats. Right and left ventricular (RV, LV) muscle and scar tissue homogenates were prepared to determine ACE activity in vitro by measuring the velocity of His-Leu release from the synthetic substrate Hyp-His-Leu. ACE activity was corrected to the tissue wet weight and is reported as nmol His-Leu g -1 min -1 . No significant change in ACE activity in the RV homogenates was demonstrable. A small nonsignificant increase of ACE activity (11 ± 9%; P>0.05) was observed 7 days after MI in the surviving left ventricular muscle. Two weeks after surgery, however, ACE activity was 46 ± 11% (P<0.05) higher in infarcted rats compared to sham-operated rats. The highest ACE activity was demonstrable in the scar tissue homogenate. In rats studied two weeks after surgery, ACE activity in the LV muscle increased from 105 ± 7 nmol His-Leu g -1 min -1 in control hearts to 153 ± 11 nmol His-Leu g -1 min -1 (P<0.05) in the remaining LV muscle of MI rats and to 1051 ± 208 nmol His-Leu g -1 min -1 (P<0.001) in the fibrous scar. These data indicate that ACE activity increased in the heart after infarction before heart failure was demonstrable by hemodynamic measurements. Since the blood vessels of the scar drain to the remaining LV myocardium, the high ACE activity present in the fibrous scar may increase the angiotensin II concentration and decrease bradykinin in the cardiac tissues surrounding the infarcted area. The increased angiotensin II in the fibrous scar may contribute to the reactive fibrosis and hypertrophy in the left ventricular muscle surviving infarction.

Synthesis and Evaluation of a Series of 99mTc(CO)3+ Lisinopril Complexes for In Vivo Imaging of Angiotensin-Converting Enzyme Expression

“…Several studies have reported increased expression of ACE in animal models of cardiac disease. ACE mRNA (24), enzyme activity (25), and protein levels identified by 125 I-MK351A (26) are demonstrated to increase in the left ventricle of rats after myocardial infarction induced by coronary artery ligation. The increase in ACE was predominantly in the border zone and scar tissue (24,25).…”

“…ACE mRNA (24), enzyme activity (25), and protein levels identified by 125 I-MK351A (26) are demonstrated to increase in the left ventricle of rats after myocardial infarction induced by coronary artery ligation. The increase in ACE was predominantly in the border zone and scar tissue (24,25). In addition, ACE mRNA increases in the left ventricle of senescent rats, which is suggested to be triggered by agerelated mechanical changes to the heart (27).…”

Remodeling in the ischemic heart: the stepwise progression for heart

“…The cardiac RAAS is activated under several pathophysiological conditions, including MI and HF of different etiologies (27,28). Angiotensinogen is produced in infarcted hearts mainly by macrophages and fibroblasts, and ACE is extensively synthesized in endothelial cells and macrophages (29).…”

“…Angiotensinogen is produced in infarcted hearts mainly by macrophages and fibroblasts, and ACE is extensively synthesized in endothelial cells and macrophages (29). ACE activity increases in all regions of the infarcted heart, particularly in the scar tissue, leading to high local Ang II concentrations (27,30). ACE inhibition in infarcted rats reduces mortality, attenuates reactive fibrosis and myocyte hypertrophy and prevents HF development (16,26,30,31).…”

Cardiac Remodeling and Angiotensin II-Forming Enzyme Activity of the Left Ventricle in Hamsters with Chronic Pressure Overload Induced by Ascending Aortic Stenosis

“…In dogs, detailed analyses have revealed that the RAS existing in cardiac tissue has a crucial role in the development of hypertrophy [2]. Cardiac ACE plays a role not only in generating Ang II, which provokes cardiac hypertrophy and fibrosis through Ang II type 1 (AT1) receptor signaling [4,12,23], but also in increasing cardiac fibrosis by catalyzing the degradation of bradykinin into inactive metabolites [3,9,26,30]. Similarly, cardiac chymase plays a role not only in converting Ang I to Ang II [31], but also in promoting direct collagen production [28,29].…”