Effects of adrenomedullin on load and myocardial performance in normal and heart-failure dogs.
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.
Lainchbury
J G
JG
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Meyer
D M
DM
Jougasaki
M
M
Burnett
J C
JC
Redfield
M M
MM
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
D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine