Cilazapril prevents cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Pharmacology

Background:

• Hyperthyroidism is associated with cardiac structural and functional changes.
• The role of the renin-angiotensin system (RAS) and sympathetic nervous system in hyperthyroid cardiomyopathy is not fully understood.

Purpose of the Study:

• To investigate the impact of hyperthyroidism on cardiac structure and post-ischemic function.
• To determine the efficacy of an angiotensin-converting enzyme (ACE) inhibitor, cilazapril, in mitigating these hyperthyroidism-induced changes.
• To elucidate the involvement of the RAS and sympathetic nervous system in hyperthyroid cardiac dysfunction.

Main Methods:

• Hyperthyroidism was induced in rats using thyroxine (T4) injections.
• Rats received either T4 alone, T4 plus cilazapril, or vehicle.
• Cardiac structure (heart weight to body weight ratio) and function (post-ischemic recovery of left ventricular pressure-rate product and cardiac work) were assessed.
• The effects of propranolol were also evaluated.

Main Results:

• T4 treatment increased blood pressure and heart weight to body weight ratio (HW:BW).
• Cilazapril normalized blood pressure and reduced HW:BW, improving post-ischemic cardiac function recovery.
• Propranolol reduced blood pressure but did not affect HW:BW or post-ischemic dysfunction.
• Cardiac work recovery was inversely correlated with HW:BW.

Conclusions:

• Thyroxine-induced cardiac hypertrophy exacerbates post-ischemic myocardial dysfunction.
• The renin-angiotensin system, not sympathetic nerve activation, plays a significant role in cardiac hypertrophy and dysfunction in hyperthyroid rats.
• ACE inhibition offers a therapeutic strategy for hyperthyroid cardiomyopathy.