Synchronization in renal microcirculation unveiled with high-resolution blood flow imaging.

Internephron interaction is fundamental for kidney function. Earlier studies have shown that nephrons signal to each other, synchronize over short distances, and potentially form large synchronized clusters. Such clusters would play an important role in renal autoregulation, but due to the technological limitations, their presence is yet to be confirmed. In the present study, we introduce an approach for high-resolution laser speckle imaging of renal blood flow and apply it to estimate the frequency and phase differences in rat kidney microcirculation under different conditions. The analysis unveiled the spatial and temporal evolution of synchronized blood flow clusters of various sizes, including the formation of large (>90 vessels) and long-lived clusters (>10 periods) locked at the frequency of the tubular glomerular feedback mechanism. Administration of vasoactive agents caused significant changes in the synchronization patterns and, thus, in nephrons' co-operative dynamics. Specifically, infusion of vasoconstrictor angiotensin II promoted stronger synchronization, while acetylcholine caused complete desynchronization. The results confirm the presence of the local synchronization in the renal microcirculatory blood flow and that it changes depending on the condition of the vascular network and the blood pressure, which will have further implications for the role of such synchronization in pathologies development.

Time-varying properties of renal autoregulatory mechanisms.

In order to assess the possible time-varying properties of renal autoregulation, time-frequency and time-scaling methods were applied to renal blood flow under broad-band forced arterial blood pressure fluctuations and single-nephron renal blood flow with spontaneous oscillations obtained from normotensive (Sprague-Dawley, Wistar, and Long-Evans) rats, and spontaneously hypertensive rats. Time-frequency analyses of normotensive and hypertensive blood flow data obtained from either the whole kidney or the single-nephron show that indeed both the myogenic and tubuloglomerular feedback (TGF) mechanisms have time-varying characteristics. Furthermore, we utilized the Renyi entropy to measure the complexity of blood-flow dynamics in the time-frequency plane in an effort to discern differences between normotensive and hypertensive recordings. We found a clear difference in Renyi entropy between normotensive and hypertensive blood flow recordings at the whole kidney level for both forced (p < 0.037) and spontaneous arterial pressure fluctuations (p < 0.033), and at the single-nephron level (p < 0.008). Especially at the single-nephron level, the mean Renyi entropy is significantly larger for hypertensive than normotensive rats, suggesting more complex dynamics in the hypertensive condition. To further evaluate whether or not the separation of dynamics between normotensive and hypertensive rats is found in the prescribed frequency ranges of the myogenic and TGF mechanisms, we employed multiresolution wavelet transform. Our analysis revealed that exclusively over scale ranges corresponding to the frequency intervals of the myogenic and TGF mechanisms, the widths of the blood flow wavelet coefficients fall into disjoint sets for normotensive and hypertensive rats. The separation of the scales at the myogenic and TGF frequency ranges is distinct and obtained with 100% accuracy. However, this observation remains valid only for the whole kidney blood pressure/flow data. The results suggest that understanding of the time-varying properties of the two mechanisms is required for a complete description of renal autoregulation.