Upregulation of adrenomedullin system in left ventricular hypertrophy of severe hypertension rats / 中华心血管病杂志

ABSTRACT

<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>