(Hypertension. 1997;30:1369-1375.)
© 1997 American Heart Association, Inc.
Articles |
Cardiac Production and Secretion of Adrenomedullin Are Increased in Heart Failure
From the Research Institute (T.N, F.Y., A.M., K.K., H.M.) and Department of Medicine (T.H., T.S., S.T.), National Cardiovascular Center, Osaka 565, Japan.
Correspondence to Toshio Nishikimi, MD, Division of Hypertension, National Cardiovascular Center, 5–7-1, Fujishirodai Suita, Osaka 565, Japan. E-mail nishikim{at}jsc.ri.ncvc.go.jp
Abstract Plasma adrenomedullin (AM) levels are reportedly increased in heart failure, but whether the cardiac production and secretion of AM is increased in heart failure remains unknown. To investigate the sites of production and secretion of AM in heart failure, we measured plasma AM levels and peptide and mRNA levels of AM in various tissues in rats with heart failure. We also examined whether the heart actually secretes AM into the circulation in patients with heart failure. We measured plasma and tissue AM levels by specific radioimmunoassay and AM mRNA by Northern blot analysis in rats with heart failure produced by aortocaval 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 heart failure rats correlated with ventricular weight. Tissue AM levels were increased in the heart and lungs but not in the kidneys or adrenals of rats with heart failure. Similarly, tissue AM mRNA levels were also 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 increased plasma atrial natriuretic peptide but not AM. These results suggest that plasma AM levels are increased in heart failure in proportion to the severity of heart failure and that cardiac production and secretion of AM is increased in heart failure rats. The lung may be another site for increased production of AM in heart failure rats. Human failing heart actually secretes AM into the circulation, and the regulation of AM secretion appears to differ from that of atrial natriuretic peptide.
Key Words: adrenomedullin • heart failure • atrial natriuretic peptide • fistula, aortocaval
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