Jensen Elisa P, Poulsen Steen S, Kissow Hannelouise, Holstein-Rathlou Niels-Henrik, Deacon Carolyn F, Jensen Boye L, Holst Jens J, Sorensen Charlotte M
Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark; and.
Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;
Am J Physiol Renal Physiol. 2015 Apr 15;308(8):F867-77. doi: 10.1152/ajprenal.00527.2014. Epub 2015 Feb 4.
Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats.
胰高血糖素样肽（GLP）-1具有一系列胰腺外效应，包括对肾脏的效应。其机制尚不清楚，但已在肾脏中鉴定出GLP-1受体。然而，关于肾脏受体的确切细胞定位描述甚少。本研究的目的是定位肾脏GLP-1受体，并描述GLP-1对肾血管系统的介导作用。我们假设肾脏GLP-1受体位于肾脏微循环中，并且这些受体的激活会影响肾脏自身调节并增加肾血流量。在啮齿动物中使用（125）I标记的GLP-1、（125）I标记的艾塞那肽-4（GLP-1类似物）和（125）I标记的艾塞那肽9-39（GLP-1受体拮抗剂）进行体内放射自显影，以定位特异性GLP-1受体结合。在麻醉大鼠中研究了GLP-1对血压、肾血流量（RBF）、心率、肾素分泌、尿流率以及钠（Na+）和钾（K+）排泄的介导作用。在离体小鼠肾脏中研究了GLP-1对入球小动脉的作用。在肾血管系统，包括入球小动脉中观察到（125）I标记的GLP-1、（125）I标记的艾塞那肽-4和（125）I标记的艾塞那肽9-39的特异性结合。在大鼠中输注GLP-1可显著增加血压、RBF和尿流率。心率和血浆肾素浓度未改变。艾塞那肽9-39抑制RBF的增加。在离体小鼠肾脏中，GLP-1和艾塞那肽-4可显著降低入球小动脉对压力逐步升高的自身调节反应。我们得出结论，GLP-1受体位于肾血管系统，包括入球小动脉中。这些受体的激活可降低入球小动脉对急性压力升高的自身调节反应，并增加正常血压大鼠的RBF。
