Internephron synchronization of renal blood flow autoregulation

Renal autoregulation is the system that maintains a constant renal blood flow when arterial pressure fluctuates. Failure of autoregulation leads to renal damage and subsequent failure. There are two mechanisms of autoregulation. First is the myogenic response, which is common to almost all microvascular beds. Second is tubuloglomerular feedback, which is a slower system that fine-tunes the delivery of solutes to each nephorn. Autoregulation is well studied. However, limitations in measurement techniques, and simplifying assumption, previously forced us to assume that all nephrons in the kidney act independently in response to local changes in blood pressure. The goal of this dissertation was to determine the presence, extent, and mechanism of network behaviour in renal autoregulation. In this dissertation I show that the mechanisms of renal autoregulation are synchronized over macroscopic regions of the renal surface, and that the spatial distribution of synchronization can be modulated by nitric oxide. Then I show that the patterns of synchronization of autoregulation on the surface of the kidney are governed by the underlying arterial anatomy. We show that the mechanism of internephron synchronization is chiefly dependent on gap junctional intercellular communication, and that removal of this communication pathway reduces the efficiency of autoregulation overall. Finally, impaired autoregulation in early diabetes is shown to coincide with a reduction in spatial smoothing of autoregulation. By the end, I have shown that internephron synchronization is present in the kidney, and 1) synchronization is modulated by an important hormonal modulator, nitric oxide, 2) that arterial anatomy determines divisions between synchronized clusters, 3) gap junctions mediate synchronization and contribute to autoregulation effectiveness, and 4) that network behaviour of autoregulation is reduced in early diabetes, linked with impaired autoregulation. Overall, this shows that internephron synchronization is an important aspect of renal autoregulation, and it must be considered in the future when studying this field.