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Discrepancy between first-dose converting enzyme inhibition at rest and subsequent inhibition during exercise in
P C Kirlin1, C Dansby, C K Laird
1Department of Medicine, College of Human Medicine, Michigan State University, East Lansing 48824.
Insights
Low-dose angiotensin-converting enzyme (ACE) inhibitors may not fully block the renin-angiotensin system during exercise in heart failure. Higher doses are needed for complete blockade during physical activity after chronic therapy.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Angiotensin-converting enzyme (ACE) inhibitors are standard therapy for chronic heart failure.
- Complete blockade of the renin-angiotensin system (RAS) is a therapeutic goal in heart failure management.
- The extent of RAS blockade by ACE inhibitors, particularly at low doses and during exercise, requires further elucidation.
Purpose of the Study:
- To compare the hemodynamic and hormonal effects of initial low-dose versus higher-dose ACE inhibitors (lisinopril or captopril) at rest.
- To assess the impact of chronic ACE inhibitor therapy on these responses during treadmill exercise testing in patients with chronic heart failure.
- To determine if initial low-dose ACE inhibition achieves complete RAS blockade during exercise.
Main Methods:
- Nine patients with chronic heart failure underwent hemodynamic and hormonal assessments at rest and during treadmill exercise.
- Measurements included systemic arterial pressure, heart rate, plasma renin activity (PRA), and plasma aldosterone concentration (PAC).
- Patients received initial low-dose and higher-dose ACE inhibitors, followed by chronic therapy for at least 4 weeks.
Main Results:
- At rest, both low and higher initial doses of ACE inhibitors produced similar changes in systemic arterial pressure, PRA, and PAC.
- During exercise after chronic therapy, dose-dependent increases in PRA and decreases in PAC were observed.
- No significant differences in exercise systemic arterial pressure or heart rate were noted between dose groups during chronic therapy.
Conclusions:
- Initial low-dose ACE inhibition effectively blocks the RAS at rest.
- Higher doses of ACE inhibitors are necessary for complete RAS blockade during exercise in patients with chronic heart failure on chronic therapy.
- These findings highlight the importance of dose titration for optimal RAS blockade in heart failure management during physical exertion.
Abstract:
Low-dose angiotensin-converting enzyme inhibition is thought to completely block the renin-angiotensin system. This study examined the hemodynamic and hormonal responses to initial low- and higher dose converting-enzyme inhibitor (lisinopril or captopril) at rest compared with the response during subsequent chronic therapy while treadmill exercise testing was performed in nine patients with chronic heart failure. At rest, similar changes in systemic arterial pressure, plasma renin activity, and plasma aldosterone concentration were found with initial low and higher doses. However, after at least 4 weeks of therapy, dose-dependent increases in plasma renin activity and decreases in plasma aldosterone concentration were noted during exercise without significant differences in exercise systemic arterial pressure or heart rate. This discrepancy suggests that initial low-dose converting enzyme inhibition does completely block the enzyme, but higher dose therapy is required for complete blockade during subsequent exercise in chronic heart failure.