Cardiovascular actions of adrenomedullin in conscious sheep. Parkes, David G. Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville VIC 3052, Australia.
APStracts 2:0145H, 1995.
Adrenomedullin (ADM) is a 52 amino acid peptide which promotes a potent vasodilator action in rats and elevates cAMP levels in isolated vascular tissue preparations. To date, the cardiovascular activity of ADM has been examined only in anesthetized animals, hence the present study examines in detail the hemodynamic actions of human ADM (1-52) in conscious, chronically instrumented sheep. Five sheep were injected intravenously with 0.1, 1, 10, 50 or 100 g ADM, and mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral conductance (TPC), coronary blood flow (CF), coronary conductance (CC), peak aortic flow (Fmax), and left ventricular dF/dt were monitored by a computer-based data collection system. ADM produced dose-dependent changes in all parameters measured, with the threshold dose being 10 g. ADM injected at 100 g rapidly and significantly decreased blood pressure by 10 1 mmHg, associated with an increase in HR of 35 4 b/min. CO increased by 1.6 0.3 l/min, whereas SV exhibited a small reduction of 11 4 ml/beat. TPC was markedly increased by 35 7 ml/min/mmHg. Changes in CF were also seen with an increase of 27 4 ml/min, and CC increased in parallel by 0.45 0.06 ml/min/mmHg, Fmax and dF/dt showed small increases of 3.8 0.8 l/min and 104 12 l/min/sec respectively. All hemodynamic parameters had returned to control values by 40 min after injection. The data suggest that ADM produces a potent vasodilator action to lower blood pressure in sheep, together with cardio -stimulatory or baroreflex effects to increase cardiac output and cardiac rate. This is the first study to report the detailed cardiovascular actions of ADM in conscious animals, and suggests that ADM may be a novel peptide involved in regulation of the cardiovascular system in mammals. 

Received 11 October 1994; accepted in final form 6 February 1995.
APS Manuscript Number H905-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.