(Hypertension. 1998;31:505.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Adrenomedullin: A Possible Autocrine or Paracrine Inhibitor of Hypertrophy of Cardiomyocytes
From the First Department of Internal Medicine, Miyazaki Medical College, Kihara, Kiyotake, Miyazaki 889-16, Japan; the *Diagnostic Science Department, Shionogi & Co., Ltd., Mishima, Settsu, Osaka 566, Japan (T.T.); and the Department of Biochemistry, National Cardiovascular Center Research Institute, Fujishinodai, Suita, Osaka 565, Japan (K.K.).
Correspondence to Tanenao Eto, MD, First Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-16, Japan
Adrenomedullin (AM), a potent vasodilator peptide, exists in the cardiac ventricle; however, the role of AM in the ventricular tissue remains unknown. In the present study, we investigated the production and secretion of AM in cultured neonatal rat cardiomyocytes, and we examined the effect of AM on de novo protein synthesis in these cells by measuring [14C]phenylalanine incorporation. The cardiomyocytes cultured with serum-free media secreted AM into the media in a time-dependent manner at the rate of 12.2±0.5 fmol/105 cells/48 hours (mean±SEM). Angiotensin II (1µmol/L) or 10% fetal bovine serum significantly (P<.01) increased the AM secretion by 115% and 305%, respectively. In addition, Northern blot analysis of total RNA extracted from the myocytes disclosed the expression of prepro-AM mRNA of 1.6 kb. Synthetic AM at 1 µmol/L significantly reduced the 10-6 mol/L angiotensin II-and 10% fetal bovine serum-stimulated [14C]phenylalanine incorporation into the cells, by 16% (P<.05) and 20% (P<.01), respectively. The inhibitory effect of AM on the angiotensin II-stimulated [14C]phenylalanine incorporation was abolished dose-dependently by a calcitonin gene-related peptide receptor antagonist, CGRP(8–37). Furthermore, blockade of the action of endogenous AM by either 10-6 mol/L CGRP(8–37) or anti-AM monoclonal antibody significantly enhanced the basal and 10-6 mol/L angiotensin II-stimulated [14C]phenylalanine incorporation. In summary, cultured neonatal rat cardiomyocytes produce and secrete AM, and the secreted AM inhibits the protein synthesis of these cells. Thus, AM may act on cardiomyocytes as an autocrine or a paracrine factor modulating the cardiac growth.
Key Words: adrenomedullin • cardiomyocytes • autocrine • paracrine • cardiac hypertrophy • monoclonal antibody
Abbreviations: AM = adrenomedullin • Ang II = angiotensin II • CGRP = calcitonin gene-related peptide • DMEM = Dulbecco’s modified Eagle’s medium • FBS = fetal bovine serum • HPLC = high-performance liquid chromatography • ir = immunoreactive • RIA = radioimmunoassay
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