Adrenomedullin augments the neurohumoral response to haemorrhage in non-pregnant but not in pregnant sheep

Adrenomedullin (ADM) is a novel peptide with actions which include reductio n of arterial pressure and interaction with a number of hormone systems. In order to assess possible interactions with the renin-angiotensin system (P AS) and the hypothalamo-pituitary-adrenal (HPA) axis, we have examined neur ohumoral responses to hypotensive haemorrhage (15 ml/kg over 15 min) with o r 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 haemorr hage in either group. In non-pregnant sheep, haemorrhage-induced activation of both RAS and HPA was significantly augmented by ADM, as indicated by gr eater 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 r esponses to haemorrhage in pregnant sheep. Rather, plasma concentrations of aldosterone (P=0.039) and adrenocorticotrophic hormone (P=0.012) were decr eased by ADM. In conclusion, ADM-induced augmentation of the RAS and HPA re sponses to hypotensive haemorrhage is abolished in the pregnant state.