title: Adrenomedullin augments the neurohumoral response to haemorrhage in non-pregnant but not in pregnant sheep.
abstract: Adrenomedullin (ADM) is a novel peptide with actions which include reduction of arterial pressure and interaction with a number of hormone systems. In order to assess possible interactions with the renin-angiotensin system (RAS) and the hypothalamo-pituitary-adrenal (HPA) axis, we have examined neurohumoral responses to hypotensive haemorrhage (15 ml/kg over 15 min) with or without co-infusions of ADM (5.5 pmol/kg per min) in six non-pregnant and eight pregnant conscious sheep. Haemorrhage induced a greater decrease in arterial pressure, but a blunted increase in heart rate in pregnant sheep. There was no significant effect of ADM on haemodynamic responses to haemorrhage in either group. In non-pregnant sheep, haemorrhage-induced activation of both RAS and HPA was significantly augmented by ADM, as indicated by greater increases in plasma renin activity (P<0.01), angiotensin II (P<0.05) and arginine vasopressin (P<0.01). In contrast, ADM did not augment these responses to haemorrhage in pregnant sheep. Rather, plasma concentrations of aldosterone (P=0.039) and adrenocorticotrophic hormone (P=0.012) were decreased by ADM. In conclusion, ADM-induced augmentation of the RAS and HPA responses to hypotensive haemorrhage is abolished in the pregnant state.
authors.affiliation: Christchurch Cardioendocrine Research Group, Christchurch School of Medicine, Christchurch, New Zealand. chris.charles@chmeds.ac.nz
authors.forename: C J
authors.initials: CJ
authors.lastname: Charles
authors.forename: M T
authors.initials: MT
authors.lastname: Rademaker
authors.forename: A M
authors.initials: AM
authors.lastname: Richards
authors.forename: M G
authors.initials: MG
authors.lastname: Nicholls
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D053607:Adrenomedullin; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D005260:Female; D006470:Hemorrhage / Q000097:blood*; D007022:Hypotension / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D023421:Models, Animal; D010455:Peptides / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012756:Sheep; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010455:Peptides; D014665:Vasodilator Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D053607:Adrenomedullin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin