Nishikimi T, Horio T, Sasaki T, Yoshihara F, Takishita S, Miyata A, Matsuo H, Kangawa K
Research Institute, National Cardiovascular Center, Suita, Osaka, Japan.
Hypertension. 1997 Dec;30(6):1369-75. doi: 10.1161/01.hyp.30.6.1369.
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.
据报道，心力衰竭患者血浆肾上腺髓质素（AM）水平升高，但心力衰竭时心脏AM的产生和分泌是否增加仍不清楚。为了研究心力衰竭时AM的产生和分泌部位，我们测量了心力衰竭大鼠各种组织中血浆AM水平以及AM的肽和mRNA水平。我们还检查了心力衰竭患者的心脏是否真的向循环系统分泌AM。我们通过特异性放射免疫测定法测量了主动脉腔静脉瘘所致心力衰竭大鼠的血浆和组织AM水平，并通过Northern印迹分析测量了AM mRNA水平。我们还测量了左心室功能不全患者在快速右心室起搏前后冠状窦和主动脉中的血浆AM水平。心力衰竭大鼠血浆AM水平的升高与心室重量相关。心力衰竭大鼠心脏和肺组织中的AM水平升高，但肾脏和肾上腺中的AM水平未升高。同样，心力衰竭大鼠心脏和肺组织中的AM mRNA水平也升高。左心室功能不全患者冠状窦中的血浆AM水平高于主动脉中的血浆AM水平。快速右心室起搏增加了血浆心房利钠肽水平，但未增加AM水平。这些结果表明，心力衰竭时血浆AM水平与心力衰竭的严重程度成比例升高，心力衰竭大鼠心脏AM的产生和分泌增加。肺可能是心力衰竭大鼠AM产生增加的另一个部位。人类衰竭心脏实际上向循环系统分泌AM，并且AM分泌的调节似乎与心房利钠肽不同。
