Abstract-Adrenomedulhn(AM), a potent vasodllator peptlde, exists m the cardiac ventricle, however, the role of AM m the ventricular tissue remams unknownIn the present study, we mvestlgated the production and secretlon of AM m cultured neonatal rat cardlomyocytes, and we exammed the effect of AM on de novo protein synthesis m these cells by measurmg ['4C] any efforts have been made to clarify the mechanisms of growth regulation of the cardiac myocardmm because of comphcatlons of the heart caused by cardiac hypertrophy At the cellular level, cardiac myocytes are known to compensate for increased workload by an Increase m their size but not m their number because these cell? are unable to dlvlde later m life ' Multiple factors such as hemodynamlc overload and humoral factors were shown to be mvolved m the process of the cardiac hypertrophy,2-4 but the detailed mechanism remams to be elucidated AM, a potent vasodllator peptlde first detected m human pheochromocytoma, has slight homology with CGRP' In addltlon to the direct vasodllator actlvlty, AM has been shown to possess a broad spectrum of blologlcal actions such as dluresls, mhlbltlon of aldosterone secretion, and mhlbltlon of prohferatlon of vascular smooth muscle cells '-* A specific RIA revealed that AM circulates m the blood and 1s present m the adrenal medulla, kidney, lung and cardiac ventricle of humans and rats ')I" The plasma AM concentration m patients with essential hypertension or primary aldosteromsm was reported to be higher than that m normotenslve control subjects, suggesting a possible role of AM m acting against further elevation of blood pressure "J' In the cardiac ventricle, AM mRNA 1s expressed at a level comparable to that of the adrenal medulla,'3b'4 and both the AM content and mRNA expression are increased m Dahl salt-sensmve and renovascular hypertensive rats compared to respective controls I516 However, at present, It remains unknown whether the cardiac myocytes secrete AM, and what the role of AM 1s m the cardiac tissueIn the first part of this study, we exammed the production and secretion of AM from cultured neonatal cardiac myocytes In the second, we investigated the effect ofAM on the de novo protein synthesis m these cells by measurmg ['4C]phenylalanme mcorporatlon, and we evaluated the action of endogenous AM by using a peptlde analogue of CGRP and anti-AM monoclonai antibody Chemicals Methods Ang II, rat AM, human

We measured plasma concentrations of adrenomedullin (AM), a novel bioactive peptide with potent vasodilator activity, in 21 patients with chronic congestive heart failure due to various heart diseases and compared them to levels in age- and sex-matched healthy subjects to examine the pathophysiological role of plasma AM in heart failure. In addition, the relationship between plasma AM and other hormones known to control the cardiovascular system was examined in these patients. The plasma AM level in the patients with heart failure was significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM, 2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of the New York Heart Association functional classification than in those in class I or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations between plasma AM and catecholamine levels, whereas the plasma AM level was significantly correlated with the concentrations of plasma atrial natriuretic peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration increased in proportion to the severity of heart failure along with the hormones known to modulate the development of congestive heart failure. The present findings suggest a possible role for AM as a circulating hormone participating in the defense mechanism against further deterioration of congestive heart failure in patients with heart disease.

No abstract

No abstract

In the biosynthesis of adrenomedullin (AM), an intermediate form, AM(1-52)-glycine-COOH (iAM), is cleaved from proAM and subsequently processed to a biologically active mature form, AM(1-52)-NH 2 (mAM), by enzymatic amidation. We recently reported that immunoreactive AM in human plasma consists of mAM and iAM. To clarify the pathophysiological roles of mAM and iAM in heart failure, we established an assay method to specifically detect mAM, and we determined the plasma concentrations of mAM and iAM in 68 patients with congestive heart failure (CHF). The plasma mAM concentrations of the CHF patients classified as being class I or II of New York Heart Association (NYHA) functional classification were significantly greater than those of the 28 healthy controls, and a further increase was noted in the class III or IV patients. Similar increases in plasma iAM were also observed in these patients compared with controls. The increased plasma mAM and iAM in 12 patients with exacerbated CHF were significantly reduced by treatment of their CHF for 7 days. In addition, the plasma concentrations of both mAM and iAM were significantly correlated with pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, cardiothoracic ratio, heart rate, and the plasma concentrations of atrial and brain natriuretic peptides in the CHF patients. Thus the plasma concentrations of both mAM and iAM were increased progressively in proportion to the severity of CHF. These results suggest that, though the role of iAM remains to be clarified, mAM acts against the further deterioration of heart failure in patients with CHF.