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 an imals in an integrative manner. Accordingly, we have examined the hemo dynamic, renal, and endocrine actions of adrenomedullin infused intrav enously at 10 and 100 ng . kg(-1) . min(-1) (each 90 min) in a vehicle -controlled study in eight normal conscious sheep. Adrenomedullin redu ced 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 4 0% (P < 0.001). Urinary sodium was reduced to 35% of control during th e 90-min clearance period immediately postinfusion (P < 0.05). Adrenom edullin 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-lower ing effects with increased cardiac output and stimulation of renin but suppressed sympathetic activation in conscious sheep. The physiologic al implications of these findings require further study.