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Inhibition of the Renin-Angiotensin System Improves Hemodynamic Function of the Diabetic Rat Heart by Restoring

Krisztina Anna Paulik1, Tamás Ivanics1, Gábor A Dunay1,2,3

  • 1Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary.

Biomedicines
|March 28, 2025
PubMed

Insights

Renin-angiotensin system (RAS) activation disrupts calcium (Ca2+i) regulation in diabetic cardiomyopathy. Inhibiting RAS with Enalapril or Losartan improves heart function and calcium handling in diabetic rats, independent of blood pressure.

Area of Science:

  • Cardiovascular Biology
  • Metabolic Diseases
  • Molecular Cardiology

Background:

  • Diabetic cardiomyopathy involves disrupted intracellular calcium (Ca2+i) regulation and renin-angiotensin system (RAS) activation.
  • Understanding the link between these factors is crucial for treating type 1 (T1D) and type 2 diabetes (T2D) complications.

Purpose of the Study:

  • To investigate the relationship between RAS activation and Ca2+i dysregulation in diabetic rat hearts.
  • To evaluate the therapeutic effects of RAS inhibition on cardiac function and Ca2+i homeostasis in T1D and T2D models.

Main Methods:

  • Induction of T1D and T2D in Sprague-Dawley rats using streptozotocin and a fructose-rich diet, respectively.
  • Treatment with Enalapril (Ena) or Losartan (Los) in T1D rats; varying doses of Ena in T2D rats.
  • Assessment of cardiac function via echocardiography, Ca2+i transients using Indo-1 fluorometry, and protein analysis via Western blot.

Main Results:

  • Diabetic rats showed impaired cardiac contractile performance, which was improved by Ena and Los treatments.
  • RAS inhibition restored impaired Ca2+i release and removal dynamics and reduced elevated diastolic Ca2+i levels.
  • Enalapril treatment prevented the decrease in SERCA2a expression and the increase in P-PLB observed in T2D hearts.

Conclusions:

  • RAS activation, likely at the tissue level, critically disrupts Ca2+i homeostasis in diabetic cardiomyopathy.
  • RAS inhibition with Enalapril or Losartan effectively mitigates these cardiac disturbances.
  • These findings highlight the potential of RAS inhibitors in managing diabetic heart failure, independent of their blood pressure-lowering effects.

Keywords:
Indo-1 surface fluorometryLangendorff heartSERCA2acardiac Ca2+i transientdiabetic cardiomyopathyenalaprillosartanrenin–angiotensin system (RAS)type 1 diabetestype 2 diabetes

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