Cardiac endothelin-1 receptors are increased in the acute phase of myocardial infarction in humans

Plasma concentration of endothelin-1 (ET-1) are increased in the acute phase of myocardial infarction and experimental studies showed that chronic ET-1 receptor antagonist administration may improve ventricular remodelling and survival. To investigate cardiac ET-1 receptors in acute myocardial infarction we studied cardiac ET-1 receptors in the hearts of 16 patients dead 1 (n=3), 3 (n=3), 7 (n=5) and 25-30 days (n=4) after acute myocardial infarction. Only patients who had not received thrombolysis or reperfusion were selected. The control group was formed by age-matched patients dead for non-cardiac reasons. ET-1 receptors on isolated cardiac membranes were investigated using binding methods with 125I-ET-1 (2000 Ci/mmol, Amersham) as radiolabeled ligand and ET-1 (0-1M) as cold displacer. Cardiac specimens were collected at necroscopy performed 24 hours after exitus. Receptor binding stability was preliminarly checked in hearts explanted from patients undergoing cardiac transplantation stored at 15°C for 12, 24 and 48 hours. Preliminary experiments performed on explanted hearts showed only a 21% increase in ET-1 receptor density at 48 h (p<0.05). In necroscopy specimens tacken in post-AMI patients ET-1 receptor density were increased by 82% at 3 days (p<0.01) and remained elevated at 30 days (+113%, p<0.01). In conclusion, cardiac ET-1 receptors sharply increases during the first week following myocardial infarction and remains elevated during the following month.