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

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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.