ABSTRACT
<p><b>OBJECTIVE</b>Levels of adrenomedullin (AM), a potent vasodilatory peptide, have been shown to increase in the early stage of acute myocardial infarction (AMI). The purpose of this study was to determine whether coronary sinus-aortic step-up of mature forms of AM is accelerated in patients with AMI after reperfusion.</p><p><b>METHODS</b>The subjects were 146 consecutive patients with a first episode of anterior AMI and 51 normal controls. All patients with AMI underwent balloon reperfusion therapy within 24 h after symptom onset. Plasma levels of two molecular forms of AM (an active, mature form [AM-m] and an intermediate, inactive glycine-extended form [AM-Gly]) in the aorta and coronary sinus (CS) were measured by specific immunoradiometric assay after reperfusion.</p><p><b>RESULTS</b>Plasma levels of AM-m and AM-Gly in the aorta and CS were higher in AMI patients than in controls. CS-aortic step-up of AM-m, which is an index of myocardial production of AM-m, was significantly greater in AMI patients than in controls [(1.7 +/- 1.4) pmol/L vs (0.4 +/- 0.3) pmol/L, P < 0.01]. However, there was no significant difference in CS-aortic step-up of AM-Gly (P = 0.30). AMI patients with left ventricular dysfunction (n = 49) had a significantly higher CS-aortic AM-m step-up than AMI patients without left ventricular dysfunction (n = 97). AMm in the aorta and CS negatively correlated with the left ventricular ejection fraction (r = -0.50, r = -0.48, P < 0.01).</p><p><b>CONCLUSION</b>Myocardial synthesis of AM-m is accelerated in patients with reperfused AMI, especially in patients with critical left ventricular dysfunction. Increased myocardial synthesis of active AM may protect against cardiac dysfunction, myocardial remodeling, or both after the onset of AMI.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adrenomedullin , Blood , Angioplasty, Balloon, Coronary , Case-Control Studies , Coronary Circulation , Myocardial Infarction , Blood , Therapeutics , Myocardial ReperfusionABSTRACT
<p><b>OBJECTIVE</b>To investigate the pathophysiological role of the cardiac adrenomedullin (AM) system, including the ligand and amidating activity in the hypertrophied heart in severe hypertension.</p><p><b>METHODS</b>The following four groups were studied: control Wistar Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), 8 weeks captopril-treated SHR-SP, and 8 weeks trichlormethiazide-treated SHR-SP. AM precursor was converted to inactive glycine-extended AM (AM-Gly) and subsequently AM-Gly was converted to active mature AM (AM-m) by enzymatic amidation. AM-m, AM-total (AM-T; AM-T = AM-m + AM-Gly), atrial natriuretic peptide (ANP) in the plasma and left ventricle (LV) by immunoradiometric assay, and gene expression of AM and ANP were measured.</p><p><b>RESULTS</b>SHR-SP had increased blood pressure, LV weight, plasma and LV ANP levels and mRNA levels of ANP compared with WKY. AM-m and AM-T levels in the plasma (AM-m: +31%; AM-T: +56%) and in the LV (AM-m: +84%; AM-T: +31%) were significantly higher in SHR-SP than those in WKY. The LV tissue AM-m/AM-T ratio was significantly higher in SHR-SP (93.2%) than that in WKY. The mRNA levels of AM in the LV were significantly higher in SHR-SP than those in WKY. Captopril and trichlormethiazide similarly decreased blood pressure and LV hypertrophy with the reduction of the LV AM-m and AM-T levels and mRNA abundance of AM.</p><p><b>CONCLUSIONS</b>These results suggested that cardiac AM system was upregulated in the hypertrophied heart in this hypertension model. Considering that AM being as an antiremodeling autocrine and(or) paracrine factor, upregulation of the AM system may modulate the pathophysiological course in LV hypertrophy.</p>