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健康男性中胰高血糖素样肽-1 的肾脏摄取及其对中枢和肾脏血液动力学的急性作用。

Renal extraction and acute effects of glucagon-like peptide-1 on central and renal hemodynamics in healthy men.

机构信息

Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen, Denmark;

Department of Endocrinology, Hvidovre University Hospital, Copenhagen, Denmark;

出版信息

Am J Physiol Endocrinol Metab. 2015 Apr 15;308(8):E641-9. doi: 10.1152/ajpendo.00429.2014. Epub 2015 Feb 10.

DOI:10.1152/ajpendo.00429.2014
PMID:25670826
Abstract

The present experiments were performed to elucidate the acute effects of intravenous infusion of glucagon-like peptide (GLP)-1 on central and renal hemodynamics in healthy men. Seven healthy middle-aged men were examined on two different occasions in random order. During a 3-h infusion of either GLP-1 (1.5 pmol·kg⁻¹·min⁻¹) or saline, cardiac output was estimated noninvasively, and intraarterial blood pressure and heart rate were measured continuously. Renal plasma flow, glomerular filtration rate, and uptake/release of hormones and ions were measured by Fick's Principle after catheterization of a renal vein. Subjects remained supine during the experiments. During GLP-1 infusion, both systolic blood pressure and arterial pulse pressure increased by 5±1 mmHg (P=0.015 and P=0.002, respectively). Heart rate increased by 5±1 beats/min (P=0.005), and cardiac output increased by 18% (P=0.016). Renal plasma flow and glomerular filtration rate as well as the clearance of Na⁺ and Li⁺ were not affected by GLP-1. However, plasma renin activity decreased (P=0.037), whereas plasma levels of atrial natriuretic peptide were unaffected. Renal extraction of intact GLP-1 was 43% (P<0.001), whereas 60% of the primary metabolite GLP-1 9-36amide was extracted (P=0.017). In humans, an acute intravenous administration of GLP-1 leads to increased cardiac output due to a simultaneous increase in stroke volume and heart rate, whereas no effect on renal hemodynamics could be demonstrated despite significant extraction of both the intact hormone and its primary metabolite.

摘要

本实验旨在阐明静脉输注胰高血糖素样肽-1(GLP-1)对健康男性中枢和肾脏血液动力学的急性影响。7 名健康中年男性在随机顺序的两种不同情况下接受检查。在 3 小时的 GLP-1(1.5 pmol·kg⁻¹·min⁻¹)或生理盐水输注期间,非侵入性估计心输出量,连续测量动脉血压和心率。通过肾静脉导管插入术,根据 Fick 原理测量肾血浆流量、肾小球滤过率以及激素和离子的摄取/释放。实验期间,受试者保持仰卧位。在 GLP-1 输注期间,收缩压和动脉脉搏压分别增加了 5±1 mmHg(P=0.015 和 P=0.002)。心率增加了 5±1 次/分钟(P=0.005),心输出量增加了 18%(P=0.016)。GLP-1 对肾血浆流量、肾小球滤过率以及 Na⁺和 Li⁺的清除率没有影响。然而,血浆肾素活性降低(P=0.037),而心房利钠肽的血浆水平不受影响。完整 GLP-1 的肾摄取率为 43%(P<0.001),而主要代谢物 GLP-1 9-36 酰胺的摄取率为 60%(P=0.017)。在人类中,急性静脉内给予 GLP-1 导致心输出量增加,这是由于每搏量和心率同时增加所致,尽管对完整激素及其主要代谢物都有明显的摄取,但对肾脏血液动力学没有影响。

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