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

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. (1) 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-l. (2) Our previous study demonstrated that morphine could activate neutrophil NEP (3) In this report we will show intravenous morphine provides cardioprotective effects in patients with heart failure by activating NEP and decreasing circulating ET-1.

METHODS

Fifty eight patients who presented with symptoms and signs of CHF and with a final diagnosis of dilated cardiomyopathy (by the World Health Organization criteria) were included for study. All the patients underwent cardiac catheterisation with haemodynamic measurements and coronary angiography to exclude other causes of CHF. They all accepted regular standard treatment for heart failure (oxygen, furosemide 1 mg/kg, and sublingual glyceryl trinitrate 0.5 mg before study) at the emergency department and were randomised into two subgroups according to the different timing of morphine administration. Those treated with protocol 1 (group lA, n = 30) underwent intravenous administration of 3 mg of morphine immediately after the first blood sampling for measurements of neutrophil NEP and ET-1. The second blood sampling was undertaken 10 minutes later. Those treated with protocol 2 (group 1B, n = 28) were checked twice for NEP and ET-l at the same time intervals but were administered morphine immediately after the se cond blood sampling. Group 2A, as …