Pericyte-mediated intra-renal blood flow regulation: from brain to kidney

肾脏通过血液过滤和随后通过选择性重吸收和分泌对滤液进行修饰的过程产生尿液。肾脏血流量高，但用于过滤而不是代谢。然而，肾脏血液供应必须满足高度调节的肾小球过滤、组织氧合和代谢清除的需要，以及肾脏维持浓缩或稀释尿液所必需的渗透梯度（从皮质到髓质）的能力。这些要求对肾内血管系统施加了不寻常的结构和排列，基本上包括2个串联的毛细血管网络：第一个是肾小球;第二个是在髓质中形成的毛细血管的线性和U形排列，以保持其高渗透压，同时确保充分的氧合和代谢清除。关于这种独特的髓质毛细血管网络的调节知之甚少，这是本申请的主题。这些毛细血管被专门的收缩细胞（周细胞）包围，我建议确定受体和介质决定其功能（从而髓血流量）使用成像和电生理方法，我已经成功地开发了类似的毛细血管结构和局部血流在中枢神经系统和视网膜。

The kidney produces urine by a process of blood filtration and subsequent modification of the filtrate by selective reabsorption and secretion. Kidney blood flow is high, but for filtration rather than metabolism. However, the kidney blood supply must fulfil the needs of highly regulated glomerular filtration, tissue oxygenation and metabolic clearance, as well as the kidney‘s ability to maintain an osmotic gradient (from cortex to medulla) necessary for it to (among other things) concentrate or dilute urine. These requirements impose an unusual structure and arrangement on the intra-renal vasculature, comprising essentially 2 capillary networks in series: the first is glomerular; the second is a linear and U-shaped arrangement of capillaries that forms in the medulla to preserve its high osmolality, while ensuring adequate oxygenation and metabolic clearance. Less is known about the regulation of this unique medullary capillary network, which is the subject of this application. These capillaries are surrounded by specialised contractile cells (pericytes); I propose to identify the receptors and mediators determining their function (and thereby medullary blood flow) using the imaging and electrophysiological approach that I have already successfully developed to study similar capillary structures and local blood flow in the CNS and retina.