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ANF 99 - 126与ANF 103 - 126对卡托普利诱导的人体肾素释放影响的比较。

Comparison of the effects of ANF 99-126 and ANF 103-126 on captopril-induced renin release in man.

作者信息

Lang C C, McMurray J J, Moyses C, Struthers A D

机构信息

Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, UK.

出版信息

Clin Endocrinol (Oxf). 1991 Jun;34(6):493-9. doi: 10.1111/j.1365-2265.1991.tb00330.x.

Abstract

OBJECTIVE

The aim was to examine the effects of atrial natriuretic factor (ANF) 99-126 and ANF 103-126, an N-terminal shortened analogue of the peptide, on the plasma renin activity response to captopril, an inhibitor of angiotensin-converting enzyme.

DESIGN

Two protocols were performed. In the first protocol, subjects were studied on three occasions. Captopril 25 mg was given and a 60 minute infusion of 5% D-glucose (placebo), or ANF 99-126 3 or 10 pmol/kg/min, was administered in a single blind randomized manner. The second protocol was divided in two parallel phases comparing ANF 103-126 either 3 or 10 pmol/kg/min to placebo.

SUBJECTS

Thirty-three salt-replete healthy male volunteers aged 21-39 years were studied in the supine position.

MEASUREMENTS

Plasma renin activity, plasma ANF 99-126 and ANF 103-126 levels, heart rate and blood pressure were measured.

RESULTS

Compared to placebo infusion, the rise in plasma renin activity after captopril was attenuated by ANF 99-126 infusion (from 755% of baseline to 294% by ANF 99-126 3 pmol/kg/min and from 755 to 202% by 10 pmol/kg/min; P less than 0.03 and P less than 0.01 respectively). The comparable findings with ANF 103-126 were 492 to 218% (3 pmol/kg/min) and 645 to 364% (10 pmol/kg/min) (P less than 0.01 and P less than 0.01 respectively).

CONCLUSIONS

The results, taken in conjunction with previous findings, suggest that atrial natriuretic factor inhibits in a non-selective manner the renin response to all secretagogues so far tested in man. The current results also suggest that the anti-renin action of atrial natriuretic factor does not depend on the first four N-terminal amino acids of the native peptide.

摘要

目的

研究心房利钠因子(ANF)99 - 126以及该肽的N端截短类似物ANF 103 - 126对血浆肾素活性(对血管紧张素转换酶抑制剂卡托普利的反应)的影响。

设计

进行了两项实验方案。在第一个方案中,对受试者进行了三次研究。给予25毫克卡托普利,并以单盲随机方式给予60分钟的5% D -葡萄糖(安慰剂)输注,或3或10皮摩尔/千克/分钟的ANF 99 - 126输注。第二个方案分为两个平行阶段,将3或10皮摩尔/千克/分钟的ANF 103 - 126与安慰剂进行比较。

受试者

33名年龄在21 - 39岁、钠储备充足的健康男性志愿者以仰卧位进行研究。

测量指标

测量血浆肾素活性、血浆ANF 99 - 126和ANF 103 - 126水平、心率和血压。

结果

与安慰剂输注相比,卡托普利给药后血浆肾素活性的升高被ANF 99 - 126输注减弱(从基线的755%降至ANF 99 - 126 3皮摩尔/千克/分钟时的294%,以及10皮摩尔/千克/分钟时的202%;P分别小于0.03和P小于0.01)。ANF 103 - 126的类似结果为492%至218%(3皮摩尔/千克/分钟)和645%至364%(10皮摩尔/千克/分钟)(P分别小于0.01和P小于0.01)。

结论

结合先前的研究结果,这些结果表明心房利钠因子以非选择性方式抑制了迄今为止在人体中测试的所有促分泌素引起的肾素反应。目前的结果还表明心房利钠因子的抗肾素作用不依赖于天然肽的前四个N端氨基酸。

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