Three peptides from the atrial natriuretic factor prohormone amino terminus lower blood pressure and produce diuresis, natriuresis, and/or kaliuresis in humans.

Three peptides from the atrial natriuretic factor prohormone amino terminus lower blood pressure and produce diuresis, natriuresis, and/or kaliuresis in humans.
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来自心房钠尿因子激素原氨基末端的三种肽可降低人体血压并产生利尿、尿钠排泄和/或排钾作用。

DOI:
10.1161/01.cir.90.3.1129
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发表时间:
1994
期刊:
影响因子:
37.8
通讯作者:
Schocken,DD
Schocken,DD
中科院分区:
医学1区
文献类型:
--
作者:
Vesely,DL;Douglass,MA;Dietz,JR;GowerJr,WR;McCormick,MT;Rodriguez-Paz,G;Schocken,DD

文献摘要

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背景由126个氨基酸的心房利钠因子前激素(proANF)的氨基酸1-30、31-67和79-98组成的三种肽在动物中具有降低血压、利尿、利钠和/或利钾尿的性质,研究了它们在人类中是否具有相似的性质。血压正常的人类志愿者(18名男性和18名女性,年龄20至58岁)根据年龄、性别、体重、血压和心率被分成6个相似的组。在60分钟的基线期后,每分钟静脉内给予100 ng proANF 1-30、31-67、79-98或ANF/kg体重,持续60分钟,随后是3小时的输注后数据收集期。每种心房利钠肽均降低收缩压和舒张压(P <0.05),proANF 31-67引起最大的降低。尿流量增加4至12倍,并且在停止proANF 1-30、31-67和79-98的相应输注后2至3小时仍显著增加(P <0.01)。心房利钠因子(ANF)使尿流量增加4- 11倍,但在输注后2小时,6例受试者中仅1例显著增加。proANF 1-30、31-67、79-98和ANF组的钠排泄量分别增加3- 8倍、3- 6倍、0- 2倍(NS)和3- 11倍。与ANF相比,proANF 1-30和31-67的利钠作用显著延长(P < .001)。ProANF 1-30、31-67、79-98和ANF分别使钾排泄增加2- 3倍、0倍、3- 4倍和2倍。高性能凝胶渗透色谱法,然后通过各自的放射免疫分析显示,proANFs 1-30,31-67,79-98,和68-98,以及ANF循环作为不同的peptide.CONCLUSIONSProANFs 1-30,31-67,和79-98,以及ANF具有显着的降压和利尿特性。ProANF 1-30和31-67在人体中也具有利钠特性,与ANF相比显著延长(P <0.001)。ProANF 79-98虽然不具有任何利钠特性,但却是四种心房利钠肽中最强的钾排泄刺激剂。
BACKGROUNDThree 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 RESULTSThirty-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.CONCLUSIONSProANFs 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.