Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen, Denmark;
Department of Endocrinology, Hvidovre University Hospital, Copenhagen, Denmark;
Am J Physiol Endocrinol Metab. 2015 Apr 15;308(8):E641-9. doi: 10.1152/ajpendo.00429.2014. Epub 2015 Feb 10.
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.
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。