CARDIOVASCULAR ACTIONS OF ADRENOMEDULLIN IN CONSCIOUS SHEEP

Adrenomedullin (Adm) is a 52-amino acid peptide that promotes a potent vasodilator action in rats and elevates adenosine 3',5'-cyclic monophosphate 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 mu g Adm, and mean arterial pressure, heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral conductance (TPC), coronary blood flow (CF), coronary conductance (CC), peak aortic flow (F-max), 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 mu g. Adm injected at 100 mu g rapidly and significantly decreased blood pressure by 10 +/- 1 mmHg, accompanied by an increase in HR of 35 +/- 4 beats/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(-1). mmHg(-1). CF showed an increase of 27 +/- 4 . ml/min, and CC increased in parallel by 0.45 +/- 0.06 ml . min(-1). mmHg(-1). F-max and dF/dt showed small increases of 3.8 +/- 0.8 l/min and 104 +/- 12 1 . min(-1). s(-1), respectively. All hemodynamic parameters had returned to control values by 40 min postinjection. The data suggest that Adm produces a potent vasodilator action to lower blood pressure in sheep, together with cardiostimulatory 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.