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

John G. Lainchbury, Donna M. Meyer, Michihisa Jougasaki, John C. Burnett, Margaret M. Redfield

Research output: Contribution to journalArticle

23 Scopus citations

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-1 iv, 100 ng·kg-1·min-1 iv, and 200 ng·kg-1·min-1 into 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 (E(es)) 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-1 intra-LV), to control for increased heart rate and sympathetic activation observed with the cumulative infusion, ADM produced arterial vasodilation but no change in E(es) or τ. In four dogs with pacing-induced heart failure, ADM (200 ng·kg-1·min-1 intra-LV) was without effect on τ, E(es), 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.

Original languageEnglish (US)
Pages (from-to)H1000-H1006
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number3 48-3
DOIs
StatePublished - Jan 1 2000

Keywords

  • Hemodynamics
  • Inotrope

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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