Enhanced endothelin-1 degradation by intravenous morphine in patients with congestive heart failure: role of neutral endopeptidase 24.11.

Endothelin-1 (ET-1), as the most potent endothelium dependent vasoconstrictor peptide, contributes to vasoconstriction, decreased ventricular function, and volume retention in congestive heart failure (CHF). Plasma ET-1 concentrations are raised in patients with CHF, correlate with symptoms and with the haemodynamic severity, and are associated with an adverse prognosis. Endothelin receptor antagonism or enhanced ET-1 hydrolysis remains the goal for treating CHF. Neutral endopeptidase 24.11 (NEP), a membrane bound zinc metalloprotease, has been shown to hydrolyse many endogenous peptides including ET-1. Our previous study demonstrated that morphine could activate neutrophil NEP. In this report we will show intravenous morphine provides cardioprotective effects in patients with heart failure by activating NEP and decreasing circulating ET-1.