Diastolic dysfunction in pressure-overload hypertrophy and its modification by angiotensin II: current concepts

Area of Science:

• Cardiology
• Molecular Biology
• Physiology

Background:

• Cardiac hypertrophy is an adaptive response to increased workload, but can lead to impaired myocardial relaxation.
• Diastolic dysfunction in hypertrophied hearts is exacerbated by ischemia and potentially influenced by the cardiac renin-angiotensin system (RAS).
• Increased cardiac angiotensin converting enzyme (ACE) activity is observed in animal models of hypertrophy.

Purpose of the Study:

• To investigate the role of cardiac ACE and angiotensin II in diastolic dysfunction in pressure-overload hypertrophy.
• To determine if inhibiting cardiac ACE can ameliorate impaired myocardial relaxation in hypertrophied hearts.
• To assess the effect of cardiac ACE inhibition on ischemia-induced diastolic dysfunction.

Main Methods:

• Utilized animal models of cardiac hypertrophy (aortic-banded rats).
• Measured cardiac ACE mRNA expression and activity.
• Assessed diastolic relaxation in isolated, perfused hearts with and without ACE inhibition.

Main Results:

• Increased cardiac ACE mRNA expression and activity were found in hypertrophied rat hearts.
• Intracardiac angiotensin II formation correlated with depressed diastolic relaxation in hypertrophied hearts.
• Specific inhibition of cardiac ACE prevented angiotensin II-induced diastolic dysfunction and improved relaxation in ischemic hypertrophied hearts.

Conclusions:

• Cardiac ACE activation contributes to diastolic dysfunction in pressure-overload hypertrophy.
• Inhibition of cardiac ACE activity represents a potential therapeutic strategy for diastolic dysfunction in hypertrophied and ischemic hearts.
• Further research is needed to elucidate the complex mechanisms underlying angiotensin II's effects on diastolic relaxation.