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

The present study was undertaken to investigate the effects of human A DM, a newly discovered peptide present in normal human plasma, as well as a fragment of human ADM, human ADM(13-52), on systemic hemodynamic s in the anesthetized cat. Intravenous (i.v.) bolus injections of huma n ADM and human ADM(13-52) decreased systemic arterial pressure (SAP) in a dose-dependent manner. Since neither peptide altered cardiac outp ut, the decreases in SAP reflect reductions in systemic vascular resis tance. The systemic vasodilator responses to the same doses of human A DM and human ADM(13-52) in the cat were similar. The present study dem onstrates 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 A DM in vivo in man. Since cardiac output and heart rate were not altere d during the marked systemic vasodepressor response to ADM, activation of the ADM vasodilator mechanism may represent a therapeutic alternat ive in the clinical management of hypertensive diseases.