title: Comparative actions of adrenomedullin and nitroprusside: interactions with ANG II and norepinephrine.
abstract: The role of adrenomedullin (ADM) in volume and pressure homeostasis remains undefined. Accordingly, we compared the biological responses to infusions of ADM and nitroprusside (NP; matched for reduction of arterial pressure) and assessed their effects on responses to ANG II and norepinephrine in eight conscious sheep. During matched falls in arterial pressure (8-10 mmHg, both P < 0.001) ADM and NP induced similar increases in heart rate. ADM increased cardiac output (P < 0.001), and the fall in calculated peripheral resistance was greater with ADM than NP (P = 0.013). ADM infusions raised plasma ADM levels (P < 0.001), plasma renin activity (P = 0.001), and ANG II (P < 0.001) but tended to blunt any concurrent rise in aldosterone compared with NP (P = 0.056). ADM maintained both urine flow (P < 0.001) and sodium excretion (P = 0.01) compared with falls observed with NP. ADM attenuated the vasopressor actions of exogenous ANG II (P = 0.006) but not norepinephrine. In addition, ADM antagonized the ANG II-induced rise in plasma aldosterone (P < 0.001). In conclusion, ADM induces a different spectrum of hemodynamic, renal, and endocrine actions to NP. These results clarify mechanisms by which ADM might contribute to volume and pressure homeostasis.
authors.affiliation: Cardioendocrine Research Group, Christchurch School of Medicine, PO Box 4345, Christchurch, New Zealand. chris.charles@chmeds.ac.nz
authors.forename: C J
authors.initials: CJ
authors.lastname: Charles
authors.forename: M G
authors.initials: MG
authors.lastname: Nicholls
authors.forename: M T
authors.initials: MT
authors.lastname: Rademaker
authors.forename: A M
authors.initials: AM
authors.lastname: Richards
mesh_terms: D053607:Adrenomedullin; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003243:Consciousness; D003404:Creatinine / Q000378:metabolism / Q000652:urine; D016232:Endothelins / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood*; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D012756:Sheep
chemical_list: D016232:Endothelins; D010455:Peptides; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009599:Nitroprusside; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D011188:Potassium; D009638:Norepinephrine