Effects of adrenomedullin on load and myocardial performance in normal and heart-failure dogs

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Abstract
Myocardial actions of the vasodilator peptide adrenomedullin (ADM) in the intact animal are unknown. Negative and positive inotropic actions have been reported in ex vivo experiments. Myocardial and load-altering actions of ADM in dogs before and after development of heart failure were studied. With controlled heart rate (atrial pacing) and after β-blockade, ADM was administered to five normal dogs in doses of 20 ng · kg−1 · min−1iv, 100 ng · kg−1 · min−1iv, and 200 ng · kg−1 · min−1into the left ventricle (LV). LV peak systolic pressure and end-systolic volume decreased with each dose of ADM. End-systolic pressure decreased with the two higher doses. At the highest dose, arterial elastance and the time constant of LV isovolumic relaxation (τ) decreased, and LV end-systolic elastance ( Ees) increased. LV end-diastolic pressure and volume were unchanged. In five additional normal dogs receiving only the highest dose of ADM (200 ng · kg−1 · min−1intra-LV), to control for increased heart rate and sympathetic activation observed with the cumulative infusion, ADM produced arterial vasodilation but no change in Eesor τ. In four dogs with pacing-induced heart failure, ADM (200 ng · kg−1 · min−1intra-LV) was without effect on τ, Ees, and systolic or diastolic pressure and volume. In vivo, ADM appears to be a selective arterial dilator without inotropic or lusitropic effects. The vasodilatory actions are attenuated in heart failure.