AN ADRENOMEDULLIN (ADM) FRAGMENT RETAINS THE SYSTEMIC VASODILATOR ACTIVITY OF HUMAN ADM

The present study was undertaken to investigate the effects of human ADM, a newly discovered peptide present in normal human plasma, as well as a fragment of human ADM, human ADM(13-52), on systemic hemodynamics in the anesthetized cat. Intravenous (i.v.) bolus injections of human ADM and human ADM(13-52) decreased systemic arterial pressure (SAP) in a dose-dependent manner. Since neither peptide altered cardiac output, the decreases in SAP reflect reductions in systemic vascular resistance. The systemic vasodilator responses to the same doses of human ADM and human ADM(13-52) in the cat were similar. The present study demonstrates the systemic vasodilator activity of ADM is conserved across species. The present data suggest that human ADM(13-52) or a peptide structurally similar to it may mediate the hemodynamic properties of ADM in vivo in man. Since cardiac output and heart rate were not altered during the marked systemic vasodepressor response to ADM, activation of the ADM vasodilator mechanism may represent a therapeutic alternative in the clinical management of hypertensive diseases.