ATRIAL-NATRIURETIC-PEPTIDE INCREASES ADRENOMEDULLIN IN THE CIRCULATION OF HEALTHY HUMANS

Adrenomedullin (ADM) is a new 52 amino acid peptide originally isolate d from extracts of human pheochromocytoma. ADM's biologic properties a re nearly identical to those of atrial natriuretic peptides. Thus, the 4 peptide hormones originating from amino acids 1-30 [long acting nat riuretic peptide], 31-67 [vessel dilator], 79-98 [kaliuretic peptide] and 99-126 [atrial natriuretic factor; ANF] of the 126 amino acid ANF prohormone as well as ADM have blood pressure lowering and diuretic pr operties. The present investigation was designed to determine if one o r more of these 4 atrial natriuretic peptides increase adrenomedullin within the circulation of healthy humans. Infusion of 100 ng/kg body w eight/minute for 60 minutes of the respective atrial peptides resulted in a 4-fold (P<0.001) increase in the circulating concentration of ad renomedullin secondary to the ANF infusion but no increase in adrenome dullin with the long acting natriuretic peptide, vessel dilator, or ka liuretic peptide infusions. The four-fold increase of adrenomedullin i n the circulation persisted throughout the infusion of ANF, but return ed to pre-infusion levels within 30 minutes of stopping the ANF infusi on. Infusion of 10 pg/kg body weight/minute for 60 minutes of ANF resu lted ina 2 1/2-fold increase (P<0.05) in the circulating concentration of adrenomedullin. There was a significant (P<0.01) diuresis and bloo d pressure lowering effect with each of the atrial natriuretic peptide s in the present investigation. This investigation suggests that 1) at rial natriuretic factor increases the release of adrenomedullin and 2) that the diuretic and blood pressure lowering effects previously attr ibuted to atrial natriuretic factor may be partially due to adrenomedu llin since both increased during the ANF infusion and both have simila r biologic effects. As opposed to atrial natriuretic factor, adrenomed ullin was not increased by long acting natriuretic peptide, vessel dil ator, or kaliuretic peptide suggesting that their biologic effects do not involve adrenomedullin.