CARDIAC PRODUCTION AND SECRETION OF ADRENOMEDULLIN ARE INCREASED IN HEART-FAILURE

Plasma adrenomedullin (AM) levels are reportedly increased in heart fa ilure, but whether the cardiac production and secretion of AM is incre ased in heart failure remains unknown. To investigate the sites of pro duction and secretion of AM in heart failure, we measured plasma AM le vels and peptide and mRNA levels of AM in various tissues in rats with heart failure. We also examined whether the heart actually secretes A M into the circulation in patients with heart failure. We measured pla sma and tissue AM levels by specific radioimmunoassay and AM mRNA by N orthern blot analysis in rats with heart failure produced by aortocava l fistula. We also measured plasma AM levels in the coronary sinus and aorta in patients with left ventricular dysfunction before and after rapid right ventricular pacing. The increase in plasma AM levels in he art failure rats correlated with ventricular weight. Tissue AM levels were increased in the heart and lungs but not in the kidneys or adrena ls of rats with heart failure. Similarly, tissue AM mRNA levels were a lso increased in the heart and lungs of heart failure rats. Plasma AM levels were higher in the coronary sinus than in the aorta in patients with left ventricular dysfunction. Rapid right ventricular pacing inc reased plasma atrial natriuretic peptide but not AM. These results sug gest that plasma AM levels are increased in heart failure in proportio n to the severity of heart failure and that cardiac production and sec retion of AM is increased in heart failure rats. The lung may be anoth er site for increased production of AM in heart failure rats. Human fa iling heart actually secretes AM into the circulation, and the regulat ion of AM secretion appears to differ from that of atrial natriuretic peptide.