Ronn Jonas, Jensen Elisa P, Wewer Albrechtsen Nicolai J, Holst Jens Juul, Sorensen Charlotte M
Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
NNF Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Physiol Rep. 2017 Dec;5(23). doi: 10.14814/phy2.13503.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor.
胰高血糖素样肽-1（GLP-1）是一种肠促胰岛素激素，可增加餐后胰岛素释放。GLP-1还可在人和啮齿动物中诱导利尿和利钠作用。在血压正常的大鼠中，GLP-1受体在肾血管树中广泛表达，急性给予GLP-1可导致平均动脉压（MAP）升高和肾血流量（RBF）增加。在高血压动物模型中，有报道称GLP-1可使MAP升高或降低。本研究的目的是检测自发性高血压大鼠（SHR）肾GLP-1受体的表达，并评估急性肾内输注GLP-1的效果。我们假设GLP-1会增加SHR的利尿和利钠作用，并降低其MAP。采用免疫组织化学染色和GLP-1受体原位杂交技术在肾脏中定位GLP-1受体。用七氟醚麻醉的血压正常的Sprague-Dawley大鼠和SHR接受了20分钟的肾内GLP-1输注，并测量了MAP、RBF、心率、尿量和尿钠排泄的变化。在正常和高血压大鼠的离体叶间动脉中评估了GLP-1的血管舒张作用。我们发现SHR的肾脏中没有GLP-1受体的表达。然而，急性肾内输注GLP-1可使两种大鼠品系的MAP、RBF、尿量和尿钠排泄增加，而不影响心率。这些结果表明，GLP-1对SHR的急性肾脏作用要么是由肾外GLP-1受体激活其他机制（如胰岛素）以诱导观察到的肾脏变化引起的，要么可能是由另一种肾GLP-1受体引起的。
