AN ADRENOMEDULLIN FRAGMENT RETAINS THE SYSTEMIC VASODEPRESSOR ACTIVITY OF RAT ADRENOMEDULLIN

The present study was undertaken to investigate the effects of human a drenomedullin, a newly discovered peptide present in normal human plas ma, as well as a fragment of adrenomedullin, on systemic hemodynamics in the anesthetized rat. Intravenous (i.v.) bolus injections of rat ad renomedullin, rat adrenomedullin-(11-50), human adrenomedullin, and hu man adrenomedullin-(13-52) decreased mean systemic arterial pressure i n a dose-dependent manner. Since rat adrenomedullin and human adrenome dullin did not decrease cardiac output, the decreases in systemic arte rial pressure reflect dose-dependent reductions in systemic vascular r esistance. The systemic vasodepressor responses to similar doses of th e adrenomedullin fragments studied and to their respective parent adre nomedullin peptides were similar. The present data demonstrate that th e entire adrenomedullin molecule is not required for full systemic vas odilator activity in vivo suggesting that rat adrenomedullin-(11-50) o r a structurally similar peptide, if formed endogenously, could mediat e the hemodynamic properties of adrenomedullin in vivo. Since rat adre nomedullin had significantly greater systemic vasodilator activity tha n human adrenomedullin at similar doses in the rat, the present data s uggest that adrenomedullin has greater systemic vasodilator activity i n its native species and that limited changes in the peptide's sequenc e confer markedly different vascular activity in vivo.