title: Hemodynamic, hormonal, and renal actions of adrenomedullin-2 in normal conscious sheep.
abstract: Although blood pressure and heart rate effects have been reported for adrenomedullin 2 (AM-2), a new member of the calcitonin gene-related peptide superfamily, little information is available regarding other biological actions of systemically administered AM-2. Accordingly, we report for the first time the integrated hemodynamic, hormonal, and renal actions of the AM-2 in normal conscious sheep. AM-2 induced significant reductions in mean arterial pressure (P < 0.001). This was associated with dose-dependent rises in heart rate (P < 0.001) and cardiac output (P < 0.001) and dose-dependent falls in calculated total peripheral resistance (P < 0.001). Right atrial pressure was increased post infusion (P = 0.026), whereas hematocrit fell post infusion (P = 0.001). AM-2 also induced significant hormonal changes, particularly in the renin-angiotensin-aldosterone system where plasma renin activity was significantly activated (P < 0.001) associated with a dose-dependent rise in plasma aldosterone (P < 0.001). Plasma cAMP also rose in response to AM-2 (P < 0.001), as did circulating levels of the natriuretic peptides, particularly post infusion. In conclusion, iv infusions of AM-2 administered to normal conscious sheep induced significant hemodynamic actions including reduced mean arterial pressure and calculated total peripheral resistance and increased heart rate and cardiac output. Concurrently, AM-2 activated plasma cAMP, plasma renin activity, aldosterone, and the natriuretic peptides. With the exception of actions on aldosterone, these actions are similar to those previously reported for AM. Thus, AM-2 may be another important regulator of volume and pressure homeostasis and may play a role in the pathophysiology of heart disease.
authors.affiliation: Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, New Zealand. chris.charles@chmeds.ac.nz
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Charles
authors.forename: Miriam T
authors.initials: MT
authors.lastname: Rademaker
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000294:innervation; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010455:Peptides / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D010455:Peptides; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D012083:Renin