Related Experiment Videos
Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure
A T Hirsch1, C E Talsness, H Schunkert
1Cardiovascular Physiology Laboratory, Brigham and Women's Hospital, Boston, Mass.
Insights
Congestive heart failure increases cardiac angiotensin converting enzyme (ACE) activity in the heart tissue, but not in circulation. This localized ACE increase correlates with myocardial infarction size in heart failure rats.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
Background:
- The renin-angiotensin system (RAS) plays a crucial role in cardiovascular homeostasis.
- Both circulating and tissue-specific RAS have been identified, but their roles in pathological conditions like heart failure are not fully understood.
Purpose of the Study:
- To investigate the activity of plasma and tissue angiotensin converting enzyme (ACE) in a rat model of compensated heart failure.
- To compare ACE activity in circulating blood versus cardiac tissue in the context of heart failure.
Main Methods:
- Experimental heart failure was induced in rats via coronary artery ligation.
- Three groups were studied: non-operated, sham-operated, and heart failure rats.
- Plasma renin concentration and ACE activity in serum, cardiac tissue (right ventricle, interventricular septum), and other organs (pulmonary, aortic, renal) were measured.
Main Results:
- Plasma renin concentration and serum ACE activity did not differ between heart failure and control groups.
- Cardiac ACE activity, specifically in the right ventricle and interventricular septum, approximately doubled in heart failure rats compared to controls.
- Pulmonary, aortic, and renal ACE activities remained unchanged in heart failure.
- A significant positive correlation was found between myocardial infarction size and right ventricular ACE activity.
Conclusions:
- Congestive heart failure is associated with a marked increase in cardiac ACE activity within the heart tissue.
- This increase in cardiac ACE activity is localized and does not affect circulating ACE levels or ACE in other major organs.
- The findings suggest a potential role for tissue-specific RAS in the pathophysiology of heart failure and its progression.
Abstract:
In addition to the circulating renin-angiotensin system, recent data demonstrate the existence of tissue renin-angiotensin systems that may be important in cardiovascular homeostasis. However, the relative activities of the circulating and tissue renin-angiotensin systems have not been examined previously in pathophysiological states, such as congestive heart failure. The present study was performed to examine the status of plasma and tissue angiotensin converting enzyme (ACE) activities in compensated experimental heart failure induced by coronary artery ligation in the rat. Three groups of male Sprague-Dawley rats were examined: 1) nonoperated rats (NO, n = 5), 2) sham-operated rats (SO, n = 5), and 3) heart failure rats (HF, n = 11). Rats were studied an averaged of 85 days postoperatively. In HF animals, plasma renin concentration and serum ACE activities were not different compared with NO and SO control animals. Cardiac ACE activity was 50% greater in the right ventricle than the interventricular septum in NO and SO rats. Both right ventricular and interventricular septal ACE activity increased approximately twofold in HF animals as compared with NO and SO groups (p less than 0.05). In contrast, pulmonary, aortic, and renal ACE activities were not altered in HF rats compared with control animals. A positive correlation existed between the histopathological size of myocardial infarction and the level of right ventricular ACE activity (r = 0.75, p less than or equal to 0.05). Such a relation between infarct size and either serum or noncardiac tissue ACE activities was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)