Regulation of cardiac adrenomedullin-mRNA in different stages of experimental heart failure

Adrenomedullin (AM) is a peptide hormone with vasodilating and natriuretic properties. AM plasma concentrations are elevated in heart failure. Whether cardiac AM-mRNA synthesis is increased in heart failure is not known. We m easured AM-mRNA/GAPDH-mRNA in all four heart chambers in compensated and ov ert heart failure in rats with two different sizes of aortocaval shunt. Lef t and right atrial AM-mRNA expressions were unchanged in both heart failure models. Similarly, left and right ventricular AM-mRNA expressions were unc hanged in compensated heart failure. In overt heart failure, however, the A M-mRNA expression was significantly increased in the left ventricle (145 +/ - 20 vs. 100 +/- 3% of control, p<0.05). The right ventricular AM-mRNA expr ession was significantly increased only in a subgroup of animals with pulmo nary congestion (lung weight >2.0 g, 141 +/- 16 vs. 100 +/- 11% of control, p<0.05). Ventricular AM concentrations were elevated in both ventricles in overt heart failure. AM plasma concentrations were significantly higher in the subgroup with pulmonary congestion than in rats with compensated heart failure (496 +/- 95 vs. 143 +/- 7 pmol/l, p<0.01). These data indicate tha t ventricular AM-mRNA expression and AM concentrations were upregulated onl y in advanced stages of heart failure. However, the exact contribution of c ardiac AM synthesis to the increased AM plasma levels remains to be establi shed.