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来自心钠素原激素氨基末端的三种肽可降低人体血压,并产生利尿、利钠和/或利钾作用。

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

作者信息

Vesely D L, Douglass M A, Dietz J R, Gower W R, McCormick M T, Rodriguez-Paz G, Schocken D D

机构信息

Department of Biochemistry, University of South Florida Health Sciences Center, Tampa.

出版信息

Circulation. 1994 Sep;90(3):1129-40. doi: 10.1161/01.cir.90.3.1129.

DOI:10.1161/01.cir.90.3.1129
PMID:8087923
Abstract

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.

摘要

背景

由126个氨基酸的心房利钠因子前体激素(proANF)的1 - 30、31 - 67和79 - 98位氨基酸组成的三种肽,在动物中具有降低血压、利尿、利钠和/或排钾特性,本研究对其在人类中是否具有相似特性进行了调查。

方法与结果

36名健康的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、血压和心率被分为六个相似的组。在60分钟的基线期后,以每分钟100 ng的proANFs 1 - 30、31 - 67、79 - 98或ANF/千克体重静脉注射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 <.05),其中proANF 31 - 67引起的降幅最大。尿流量增加4至12倍,在停止分别输注proANFs 1 - 30、31 - 67和79 - 98后2至3小时仍显著增加(P <.01)。心房利钠因子(ANF)使尿流量增加4至11倍,但输注后2小时仅6名受试者中的1名显著增加。钠排泄分别增加3至8倍、3至6倍、0至2倍(无统计学意义)和3至11倍,分别对应proANFs 1 - 30、31 - 67、79 - 98和ANF。与ANF相比,proANFs 1 - 30和31 - 67的利钠作用显著延长(P <.001)。proANFs 1 - 30、31 - 67、79 - 98和ANF分别使钾排泄增加2至3倍、0倍、3至4倍和2倍。高效凝胶渗透色谱法随后进行各自的放射免疫测定显示,proANFs 1 - 30、31 - 67、79 - 98和68 - 98以及ANF作为不同的肽循环存在。

结论

proANFs 1 - 30、31 - 67和79 - 98以及ANF具有显著的降压和利尿特性。proANFs 1 - 30和31 - 67在人类中也具有利钠特性,与ANF相比显著延长(P <.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排钾刺激剂。

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Three peptides from the atrial natriuretic factor prohormone amino terminus lower blood pressure and produce diuresis, natriuresis, and/or kaliuresis in humans.来自心钠素原激素氨基末端的三种肽可降低人体血压,并产生利尿、利钠和/或利钾作用。
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