Hemodynamic, hormonal, and renal effects of adrenomedullin in conscious sheep

Adrenomedullin is a recently discovered peptide that 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-1.min-1 (each 90 min) in a vehicle-controlled study in eight normal conscious sheep. Adrenomedullin reduced right atrial pressure (P < 0.05) and diastolic (15 mmHg, P < 0.01) and mean arterial pressure (10 mmHg, P < 0.05) and increased cardiac output (3 l/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 postinfusion (P < 0.05). Adrenomedullin increased plasma adenosine 3',5'-cyclic monophosphate levels (P < 0.001). Plasma renin activity was elevated during adrenomedullin (P < 0.001) coincident with the peak hypotensive effect, whereas plasma aldosterone was not affected 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 require further study.