Circulation, Vol 90, 1129-1140, Copyright © 1994 by American Heart Association
DL Vesely, MA Douglass, JR Dietz, WR Gower Jr, MT McCormick, G Rodriguez-Paz and DD Schocken
BACKGROUND: Three peptides consisting of amino acids 1-30, 31-67, and 79-98
of the 126-amino acid atrial natriuretic factor prohormone (proANF), which
have blood pressure-lowering, diuretic, natriuretic, and/or kaliuretic
properties in animals, were investigated to determine if they have similar
properties in humans. METHODS AND RESULTS: Thirty- six healthy,
normotensive human volunteers (18 men and 18 women, ages 20 to 58 years)
were divided into six similar groups based on age, sex, weight, 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 was given
intravenously for 60 minutes followed by a 3-hour postinfusion data
collection period. Each of the atrial natriuretic peptides decreased
systolic and diastolic blood pressures (P < .05), with proANF 31-67
causing the largest decrease. Urine flow increased 4- to 12-fold and was
still significantly increased (P < .01) for 2 to 3 hours after stopping
the respective infusions of proANFs 1-30, 31-67, and 79-98. Atrial
natriuretic factor (ANF) increased urine flow 4- to 11-fold but by 2 hours
after infusion was significantly increased in only 1 of 6 subjects. Sodium
excretion increased 3- to 8-fold, 3- to 6- fold, 0- to 2-fold (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 significantly 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. High-performance gel permeation chromatography
followed by the respective radioimmunoassays revealed that proANFs 1-30,
31-67, 79-98, and 68-98, as well as ANF circulate as distinct 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 stimulator of
potassium excretion of the four atrial natriuretic peptides.
ARTICLES
Three peptides from the atrial natriuretic factor prohormone amino terminus lower blood pressure and produce diuresis, natriuresis, and/or kaliuresis in humans
Department of Biochemistry, University of South Florida Health Sciences Center, Tampa.
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