Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

Area of Science:

• Cardiovascular Physiology
• Neuropharmacology
• Molecular Cardiology

Background:

• Myocardial opioid receptors are present in humans and animals.
• These receptors colocalize with calcium channels involved in cardiac excitation-contraction coupling in the left ventricle.
• The role of the cardiac opioid system in heart failure is not fully understood.

Purpose of the Study:

• To investigate the effect of naltrexone, an opioid receptor antagonist, on cardiac function and neurohumoral parameters.
• To examine these effects in Wistar rats experiencing volume overload-induced heart failure.

Main Methods:

• Volume overload heart failure was induced in Wistar rats via an aortocaval fistula (ACF).
• Cardiac opioid receptors and their mRNA, along with endogenous ligand mRNA, were quantified.
• Rats received naltrexone or vehicle for 28 days, with hemodynamic and humoral parameters assessed.

Main Results:

• Naltrexone treatment reduced central venous pressure and left ventricular end-diastolic pressure.
• Systolic and diastolic left ventricular functions were improved by naltrexone.
• Plasma levels of rat brain natriuretic peptide and angiotensin-2 decreased, alongside reduced opioid receptor mRNA and increased endogenous opioid peptide mRNA.

Conclusions:

• Opioid receptor blockade with naltrexone improves left ventricular function in heart failure.
• Naltrexone reduces neurohumoral markers (rBNP-45, angiotensin-2) and downregulates cardiac opioid receptor mRNA.
• These findings suggest a potentially cardiodepressant role for the cardiac opioid system during volume overload heart failure.