3 PEPTIDES FROM THE ATRIAL-NATRIURETIC-FACTOR PROHORMONE AMINO-TERMINUS LOWER BLOOD-PRESSURE AND PRODUCE DIURESIS, NATRIURESIS, AND OR KALIURESIS IN HUMANS/

Background Three peptides consisting of amino acids 1-30, 31-67, and 7 9-98 of the 126-amino acid atrial natriuretic factor prohormone (proAN F), which have blood pressure-lowering, diuretic, natriuretic, and/or kaliuretic properties in animals, were investigated to determine if th ey have similar properties in humans. Methods and Results Thirty-six h ealthy, normotensive human volunteers (18 men and 18 women, ages 20 to 58 years) were divided into six similar groups based on age, sex, wei ght, blood pressure, and heart rate. After a 60-minute baseline period , 100 ng of proANFs 1-30, 31-67, 79-98, or ANF/kg body wt per minute w as given intravenously for 60 minutes followed by a 3-hour postinfusio n data collection period. Each of the atrial natriuretic peptides decr eased systolic and diastolic blood pressures (P<.05), with proANF 31-6 7 causing the largest decrease. Urine flow increased 4- to 12-fold and was still significantly increased (P<.01) for 2 to 3 hours after stop ping the respective infusions of proANFs 1-30, 31-67, and 79-98. Atria l natriuretic factor (ANF) increased urine flow 4-to 11-fold but by 2 hours after infusion was significantly increased in only 1 of 6 subjec ts. Sodium excretion increased 3- to 8-fold, 3- to 6-fold, 0- to 2-fol d (NS), and 3- to 11-fold, respectively, with proANFs 1-30, 31-67, 79- 98, and ANF. Natriuretic effects of proANFs 1-30 and 31-67 were signif icantly prolonged (P<.001) compared with ANF. ProANFs 1-30, 31-67, 79- 98, and ANF increased potassium excretion 2- to 3-fold, 0-fold, 3- to 4-fold, and 2-fold, respectively. Highperformance gel permeation chrom atography followed by the respective radioimmunoassays revealed that p roANFs 1-30, 31-67, 79-98, and 68-98, as well as ANF circulate as dist inct peptides. Conclusions ProANFs 1-30, 31-67, and 79-98, as well as ANF have significant blood pressure-lowering and diuretic properties. ProANFs 1-30 and 31-67 also have natriuretic properties in humans that are significantly (P<.001) prolonged compared with ANF. ProANF 79-98, although not possessing any natriuretic property, is the strongest st imulator of potassium excretion of the four atrial natriuretic peptide s.