Analysis and Modelling of Multimodal Interactions in Renal Autoregulation

By maintaining the volume and composition of the body fluids within narrow bounds and by producing a set of hormones that affect the blood vessels, the kidneys provide important long-term regulation of the blood pressure. Disturbances of kidney function can cause hypertension, a prevalent disease in modern societies. The kidneys protect their own function against short-term variations in the blood pressure. At the level of the individual functional unit (the nephron), pressure and flow control involves two different mechanisms: the tubuloglomerular feedback, which regulates the incoming blood flow in response to variations of the NaCl concentration of the tubular fluid near the terminal point of the loop of Henle (macula densa), and a myogenic mechanism by which the afferent arteriole regulates its diameter in response to variations in its transmural pressure. Experimentally, both of these mechanisms are found to produce oscillations. In the present study, analysis of experimental data of the tubular pressure and arteriole blood flow in combination with mechanism-based modelling has been used to answer the following questions: (i) How to reveal and characterize interactions between the two mechanisms of renal autoregulation? (ii) To what extend does nephron-to-nephron communication lead to cooperative behaviour? and (iii) How do intra- and inter-nephron interactions differ in normotensive and hypertensive rats? Analysis of experimental data revealed the presence of amplitude and frequency modulation, i.e. the regulation is provided not only by a change in the diameters of the active parts of the vessels, but also by an adjustment of the frequency of the myogenic oscillations. Interaction between the two mechanisms of renal autoregulation was found to be significantly stronger in spontaneously hypertensive rats than in normotensive rats. Synchronization phenomena in neighbouring nephrons were evaluated by measuring both frequency and phase entrainment. Statistical analysis showed that synchronization among mechanisms of renal autoregulation is reduced in hypertensive rats. With a probability exceeding 80%, normotensive rats demonstrated full entrainment in neighbouring nephrons where the oscillatory modes associated with two mechanisms of autoregulation were synchronized. Hypertensive rats displayed about half the probability of full synchronization and about twice the probability of partial synchronization, i.e. a state where neighbouring nephrons synchronize their slow tubuloglomerular feedback dynamics, while the fast myogenic dynamics remain desynchronized, or vice versa. Spontaneously hypertensive rats generally remained in synchrony for only 1/3 to 1/2 as long as the normotensive ones. Numerical simulations with a model of superficial nephrons connected via a flow mediated hemodynamic coupling and a vascular propagated coupling reproduced the experimentally observed patterns of behaviour. Lack of synchronization may be responsible for the development of irregular dynamics in the tubules of rats with experimental hypertension. The model has been extended by including deep nephrons for which it has not yet been possible to perform similar experimental measurements. Using available anatomical and physiological information we constructed a model of an nephron-vascular ensemble including superficial as well as deep nephrons with different length of loop of Henle. The computer simulation suggested that irregular dynamics of nephron ensemble increases at higher arterial pressures and values of the coupling strength. The model showed that, for physiologically reasonable parameter values, the deep nephrons do not synchronize with the superficial nephrons even though they are coupled via the same blood supply

Modeling of Kidney Hemodynamics: Probability-Based Topology of an Arterial Network

Through regulation of the extracellular fluid volume, the kidneys provide important long-term regulation of blood pressure. At the level of the individual functional unit (the nephron), pressure and flow control involves two different mechanisms that both produce oscillations. The nephrons are arranged in a complex branching structure that delivers blood to each nephron and, at the same time, provides a basis for an interaction between adjacent nephrons. The functional consequences of this interaction are not understood, and at present it is not possible to address this question experimentally. We provide experimental data and a new modeling approach to clarify this problem. To resolve details of microvascular structure, we collected 3D data from more than 150 afferent arterioles in an optically cleared rat kidney. Using these results together with published micro-computed tomography (μCT) data we develop an algorithm for generating the renal arterial network. We then introduce a mathematical model describing blood flow dynamics and nephron to nephron interaction in the network. The model includes an implementation of electrical signal propagation along a vascular wall. Simulation results show that the renal arterial architecture plays an important role in maintaining adequate pressure levels and the self-sustained dynamics of nephrons

Raman Scattering:From Structural Biology to Medical Applications

This is a review of relevant Raman spectroscopy (RS) techniques and their use in structural biology, biophysics, cells, and tissues imaging towards development of various medical diagnostic tools, drug design, and other medical applications. Classical and contemporary structural studies of different water-soluble and membrane proteins, DNA, RNA, and their interactions and behavior in different systems were analyzed in terms of applicability of RS techniques and their complementarity to other corresponding methods. We show that RS is a powerful method that links the fundamental structural biology and its medical applications in cancer, cardiovascular, neurodegenerative, atherosclerotic, and other diseases. In particular, the key roles of RS in modern technologies of structure-based drug design are the detection and imaging of membrane protein microcrystals with the help of coherent anti-Stokes Raman scattering (CARS), which would help to further the development of protein structural crystallography and would result in a number of novel high-resolution structures of membrane proteins—drug targets; and, structural studies of photoactive membrane proteins (rhodopsins, photoreceptors, etc.) for the development of new optogenetic tools. Physical background and biomedical applications of spontaneous, stimulated, resonant, and surface- and tip-enhanced RS are also discussed. All of these techniques have been extensively developed during recent several decades. A number of interesting applications of CARS, resonant, and surface-enhanced Raman spectroscopy methods are also discussed

STRUCTURE AND PROPERTIES OF ATTRACTORS IN NON-AUTONOMOUS AND CONNECTED DYNAMIC SYSTEMS

The aim is to searh the general regularities of the forced, intermutual and spatial synchronization for wide class of the dynamic systems and also to reveal the special features stipulated with their natural complex dynamics; to investigate the possible ways of the transfer from ergodic quasi-periodical oscillations to the chaotic ones. The special features of the dynamic transfer to the chaotic synchronization problem in the non-autonomous and connected systems in the which the chaotic attractors of complex structure are realized have been investigated firstly. The regularities of damaging ergodic quasi-periodical oscillations through formation of the strange non-chaotic attractor have been discovered firstly and investigated numerically. The obtained results are used in the educational process at the Saratov State UniversityAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio