title: Effects of adrenomedullin on load and myocardial performance in normal and heart-failure dogs.
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 beta-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 (tau) 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 tau. In four dogs with pacing-induced heart failure, ADM (200 ng. kg(-1). min(-1) intra-LV) was without effect on tau, 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.
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Lainchbury
authors.forename: D M
authors.initials: DM
authors.lastname: Meyer
authors.forename: M
authors.initials: M
authors.lastname: Jougasaki
authors.forename: J C
authors.initials: JC
authors.lastname: Burnett
authors.forename: M M
authors.initials: MM
authors.lastname: Redfield
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D000242:Cyclic AMP / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000097:blood; D010455:Peptides / Q000008:administration & dosage* / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine