Romero Cesar A, Carretero Oscar A
Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital , Detroit, Michigan.
Am J Physiol Renal Physiol. 2019 Jun 1;316(6):F1218-F1226. doi: 10.1152/ajprenal.00381.2018. Epub 2019 Mar 6.
Afferent arteriole (Af-Art) diameter regulates pressure and flow into the glomerulus, which are the main determinants of the glomerular filtration rate. Thus, Af-Art resistance is crucial for Na filtration. Af-Arts play a role as integrative centers, where systemic and local systems interact to determine the final degree of resistance. The tubule of a single nephron contacts an Af-Art of the same nephron at two locations: in the transition of the thick ascending limb to the distal tubule (macula densa) and again in the connecting tubule. These two sites are the anatomic basis of two intrinsic feedback mechanisms: tubule-glomerular feedback and connecting tubule-glomerular feedback. The cross communications between the tubules and Af-Arts integrate tubular Na and water processing with the hemodynamic conditions of the kidneys. Tubule-glomerular feedback provides negative feedback that tends to avoid salt loss, and connecting tubule-glomerular feedback provides positive feedback that favors salt excretion by modulating tubule-glomerular feedback (resetting it) and increasing glomerular filtration rate. These feedback mechanisms are also exposed to systemic modulators (hormones and the nervous system); however, they can work in isolated kidneys or nephrons. The exaggerated activation or absence of any of these mechanisms may lead to disequilibrium in salt and water homeostasis, especially in extreme conditions (e.g., high-salt diet/low-salt diet) and may be part of the pathogenesis of some diseases. In this review, we focus on molecular signaling, feedback interactions, and the physiological roles of these two feedback mechanisms.
入球小动脉（Af-Art）的直径调节进入肾小球的压力和流量，而压力和流量是肾小球滤过率的主要决定因素。因此，入球小动脉阻力对钠滤过至关重要。入球小动脉作为整合中心，全身系统和局部系统在此相互作用以确定最终的阻力程度。单个肾单位的肾小管在两个位置与同一肾单位的入球小动脉接触：在髓袢升支粗段向远曲小管的过渡处（致密斑）以及在连接小管处。这两个部位是两种内在反馈机制的解剖学基础：肾小管-肾小球反馈和连接小管-肾小球反馈。肾小管和入球小动脉之间的交叉通讯将肾小管对钠和水的处理与肾脏的血流动力学状况整合在一起。肾小管-肾小球反馈提供负反馈，倾向于避免盐分流失，而连接小管-肾小球反馈提供正反馈，通过调节肾小管-肾小球反馈（使其重置）并增加肾小球滤过率来促进盐分排泄。这些反馈机制也受到全身调节剂（激素和神经系统）的影响；然而，它们可以在离体肾脏或肾单位中发挥作用。这些机制中任何一种的过度激活或缺失都可能导致盐和水平衡的失衡，尤其是在极端情况下（例如，高盐饮食/低盐饮食），并且可能是某些疾病发病机制的一部分。在本综述中，我们重点关注这两种反馈机制的分子信号传导、反馈相互作用和生理作用。
