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Published on: May 26, 2022
Activation of angiotensin-converting enzyme 2 improves cardiac electrical changes in ventricular repolarization in
Danielle C O Coutinho1, Gustavo Monnerat-Cahli2, Anderson J Ferreira3
1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, 6627-31.270-901, Belo Horizonte, MG, Brazil.
Aims:
Diabetic patients present a high level of cardiac arrhythmias and risk of cardiac sudden death. The renin-angiotensin system (RAS) plays a key role in diabetes and cardiac diseases. The present study aimed to evaluate whether an angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), could improve the streptozotocin (STZ)-induced electrical changes in ventricular repolarization in hyperglycaemic rats.
Methods And Results:
Hyperglycaemia was induced in Wistar male rats with STZ (60 mg/kg/iv). After 4 weeks of STZ injection, rats were daily treated with saline (control) or DIZE (1 mg/kg/gavage) for four consecutive weeks. The cardiac electrical function was evaluated in vivo by electrocardiogram and in vitro by cardiac action potential records in different pacing frequencies. Treatment with DIZE was not able to reverse hyperglycaemia nor body weight loss. However, DIZE reversed hyperglycaemia-induced cardiac electrical changes in ventricular repolarization. Specifically, animals treated with DIZE showed shorter QT and QTc intervals. In addition, ACE2 activation was capable to shorten the cardiac action potential and also reverse the arrhythmic markers. Diminazene aceturate treatment did not induce arrhythmic events in normal, as well as in hyperglycaemic animals.
Conclusion:
Our data indicate that activation of ACE2 has a beneficial effect in hyperglycaemic rats, improving the cardiac electrical function. Thus, DIZE represents a promising new therapeutic agent to treat hyperglycaemia-induced cardiac electrical changes in ventricular repolarization.
Insights
Diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, improved cardiac electrical function in hyperglycaemic rats. DIZE shortened ventricular repolarization times and reversed arrhythmia markers without causing adverse effects, suggesting therapeutic potential.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Diabetic patients have increased risks of cardiac arrhythmias and sudden death.
- The renin-angiotensin system (RAS) is implicated in diabetes and cardiac conditions.
- Hyperglycaemia can induce detrimental electrical changes in the heart.
Purpose of the Study:
- To investigate the effect of diminazene aceturate (DIZE), an ACE2 activator, on cardiac electrical changes in streptozotocin (STZ)-induced hyperglycaemic rats.
- To assess DIZE's potential to mitigate STZ-induced ventricular repolarization abnormalities.
Main Methods:
- Hyperglycaemia was induced in Wistar rats using STZ (60 mg/kg/iv).
- Rats were treated daily with saline (control) or DIZE (1 mg/kg/gavage) for four weeks.
- Cardiac electrical function was assessed using electrocardiography and cardiac action potential recordings.
Main Results:
- DIZE treatment did not reverse hyperglycaemia or body weight loss.
- DIZE significantly shortened QT and QTc intervals in hyperglycaemic rats.
- ACE2 activation by DIZE shortened cardiac action potential duration and reversed arrhythmia markers without inducing arrhythmias.
Conclusions:
- Activation of ACE2 with DIZE demonstrates a beneficial effect on cardiac electrical function in hyperglycaemic rats.
- DIZE shows promise as a therapeutic agent for managing hyperglycaemia-related cardiac electrical disturbances.
- Targeting ACE2 may offer a novel strategy for preventing cardiac complications in diabetes.
