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Angiotensin-converting enzyme inhibition and salt in experimental myocardial infarction
K Yoshida1, M Kohzuki, D J Casley
1Section of Internal Medicine and Disability Prevention, Disability Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
Insights
Angiotensin-converting enzyme inhibitors reduce cardiac hypertrophy post-myocardial infarction. Their beneficial effects stem primarily from lowering blood pressure, not directly inhibiting cardiac enzyme activity, as shown in a rat model.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Angiotensin-converting enzyme (ACE) inhibitors are known to reduce ventricular hypertrophy following myocardial infarction (MI).
- Cardiac ACE activity increases in rat models of MI, suggesting a potential target for therapeutic intervention.
Purpose of the Study:
- To differentiate the mechanisms by which ACE inhibitors attenuate cardiac hypertrophy after MI.
- To determine if the benefits are mediated by reduced ventricular afterload or direct inhibition of cardiac ACE.
Main Methods:
- A rat model of myocardial infarction was used.
- Animals were treated with vehicle, perindopril (an ACE inhibitor), or perindopril with high sodium intake (1% saline) for 6 weeks.
- Blood pressure, cardiac hypertrophy, and cardiac ACE activity were measured.
Main Results:
- Perindopril treatment reduced blood pressure and prevented cardiac hypertrophy.
- Perindopril also inhibited cardiac ACE activity.
- Concurrent sodium loading abolished the effects of perindopril on blood pressure and cardiac hypertrophy.
- Sodium loading did not affect the degree of cardiac ACE inhibition by perindopril.
Conclusions:
- The antihypertrophic effects of perindopril in the post-MI rat model are primarily attributed to blood pressure reduction (afterload reduction).
- Direct inhibition of cardiac ACE activity by perindopril plays a lesser role in preventing cardiac hypertrophy in this context.
Abstract:
It is well known that angiotensin-converting enzyme inhibitors attenuate progressive ventricular enlargement or hypertrophy after myocardial infarction and that cardiac angiotensin-converting enzyme activity is increased in the rat model of myocardial infarction. In this study, to determine whether the beneficial effects of angiotensin-converting enzyme inhibition on cardiac hypertrophy after myocardial infarction are due to a reduction in ventricular afterload or to inhibition of cardiac angiotensin-converting enzyme, we used sodium loading during angiotensin-converting enzyme inhibition. The rat model of myocardial infarction was treated with a vehicle, 1% saline, as drinking fluid, perindopril (2 mg/kg/day), or 1% saline as drinking fluid plus perindopril (2 mg/kg/day) for 6 weeks. Perindopril reduced blood pressure, prevented cardiac hypertrophy, and inhibited cardiac angiotensin-converting enzyme. The effects of perindopril on blood pressure and cardiac hypertrophy were abolished by sodium loading, which did not alter the degree of cardiac angiotensin-converting enzyme inhibition. Thus the actions of perindopril on cardiac hypertrophy depend more on blood pressure reduction than on cardiac angiotensin-converting enzyme inhibition in the rat model of myocardial infarction.