Hemodynamic, hormonal and renal effects of adrenomedullin in
conscious sheep..
Charles, Christopher J., Miriam T. Rademaker, A. Mark Richards, Garth
J. S. Cooper, David H. Coy, Ning-Yi Jing, M. Gary Nicholls.
Department of Medicine, Christchurch School of Medicine,
Christchurch, NEW ZEALAND, Department of Medicine, School of Medicine
and Developmental Biology and Cancer Research Group, School of
Biological Sciences, University of Auckland, Auckland, NEW ZEALAND
and 4Department of Medicine, Tulane University, New Orleans, USA
APStracts 3:0414R, 1996.
Adrenomedullin is a recently discovered peptide which has been shown
to reduce arterial pressure and induce natriuresis. However, few
studies have examined the biological actions of adrenomedullin in
conscious animals in an integrative manner. Accordingly, we have
examined the hemodynamic, renal and endocrine actions of
adrenomedullin infused intravenously at 10 and 100 ng/kg/min (each
90min) in a vehicle controlled study in eight normal conscious sheep.
Adrenomedullin reduced right atrial pressure (p<0.05),
diastolic (15mmHg, p<0.01) and mean arterial pressure (10
mmHg, p<0.05) and increased cardiac output (3l/min,
p<0.001). Total peripheral resistance was reduced 40%
(p<0.001). Urinary sodium was reduced to 35 % of control
during the 90 min clearance period immediately post-infusion
(p<0.05). Adrenomedullin increased plasma cyclic AMP levels
(p<0.001). Plasma renin activity was elevated during
adrenomedullin (p<0.001) co-incident with the peak hypotensive
effect whilst plasma aldosterone was not effected and plasma
norepinephrine levels fell (p<0.05). In conclusion,
adrenomedullin had clear blood pressure lowering effects with
increased cardiac output and stimulation of renin but suppressed
sympathetic activation in conscious sheep. The physiological
implications of these findings requires further study.
Received 16 July 1996; accepted in final form 12 November 1996.
APS Manuscript Number R402-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996