Diabetes mellitus is a metabolic disorder syndrome caused by various pathogenic factors leading to imbalance of active substance secretion and endothelial dysfunction, causing macro and micro vascular complications. As the most important signal transduction molecule released by endothelium, NO participates in various physiological processes of microcirculation and plays an important role in vascular relaxation regulation. Extensive studies focus on the investigation of the analysis of NO transport in microvessels, RBC motion and its influence on NO transport since they are of extremely importance for understanding the mechanisms of vessel autoregulation and microcirculation lesion. NO transport characteristics are closely associated with hemorheology, hemodynamics and microvascular structure. Nevertheless, up to date, there are limited reports on NO transport characteristics in diabetic mellitus. The purpose of this review is to summarize the current advances in the investigation of NO transport characteristics from cellular to vascular level, which can provide effective ideas for the early diagnosis of vascular complications in diabetes.

The aim of this study was to explore changes in the microvascular tone as measured by laser Doppler flowmetry (LDF) and the microcirculation structure of the dorsal skin of rats with type 2 diabetes mellitus. The diabetic rat model was induced by a diet of high-sugar and high-lipid fodder combined with the injection of streptozotocin into the abdominal cavity. Depending on the interval between the development of diabetes and the experiments, the diabetic rats were subdivided into three groups. The evaluation of microvascular tone was based on the amplitude responses of the LDF signal fluctuations in the appropriate frequency range in the dorsal skin of the rats during a thermal test (at 42 °C). The nitric oxide (NO) level in plasma was also used as a marker of endothelial dysfunction. Changes in the microcirculation structure in the diabetic rats were estimated by measuring the microvascular density in the choke vessels of the dorsal skin of the rats. The experimental results with respect to red blood cell (RBC)–related parameters showed decreased hematocrit and hemoglobin levels and increased standard deviation of the width of the RBC distribution in three diabetic rats. The increasing fluctuation amplitudes diminished in the endothelial frequency range in response to the thermal test and this was accompanied by abnormal NO levels in plasma of the diabetic groups as compared with healthy rats. A significant reduction in the microvascular density of the choke vessels of the dorsal skin was found only in the diabetic group at the most advanced stage of diabetes in this experiment. Thus, we suggest that endothelial dysfunction occurs in diabetic rats and changes in the microcirculation structure of the dorsal skin occur in a later stage of diabetes development. A. Photograph of measurement method by using a LDF probe and heating device in the dorsal skin of the rat. B. Dorsal skin LDF signals of a healthy rat during the thermal stimuli test. (a) Blood flow signal record for the test. Wavelet filtration of blood flow signal in (b) myogenic range, (c) neurogenic range, and (d) endothelial range

It is pivotal that endothelium-dependent Nitric Oxide (NO) consumed by hemoglobin (Hb) inside red blood cells (RBCs) membrane, regulates the vascular tone. The whole processes of NO transport in vessel containing flowing RBCs is still not clear, such as NO production in endothelium, diffusion in plasma and consumption inside RBCs. In this work, the motion of RBCs in a microvessel is investigated by using immersed boundary lattice Boltzmann method (IB-LBM) first and the deformability of RBCs is expressed by using spring network model which is based on the minimum energy principle. Furthermore, the interaction between RBCs is considered. Based on the wall shear stress (WSS), NO production rate originated from endothelium was obtained by using a hyperbolic model. NO distribution inside the microvessel with multiple RBCs was computed by using immersed boundary finite difference method (IB-FDM). The result shows that a large (small) WSS exists at locations with a relatively wide(narrow) gap between the wall and cell. In terms of mass transfer, an increase of RBC membrane permeability leads to a decrease of NO concentration in the vessel and the surrounding endothelium significantly. In addition, with the increasing of hematocrit (Hct) value, NO concentration distribution in the whole vessel decreases both in the lumen and vascular wall. Finally, the thickness of RBCs-depleted layer gradually decreases with the weakened deformability of RBCs membrane, and the change degree of cell free layer (CFL) thickness decreases as the bending stiffness is relatively higher. Thus, when bending stiffness is higher, the NO concentration in vascular wall is reduced resulting from the thinner CFL.

The endothelial dysfunction and the unbalanced secretion of vasoactive substances are the main causes of the macro and micro vascular complications for patients with diabetic mellitus (DM). This paper investigates the blood flow and the nitric oxide (NO) transport in a permeable capillary by using a finite element method. The computational domain consists of a permeable straight or bifurcated capillary and the surrounding tissue with different endothelial hydraulic permeability. The blood flow in the lumen of a capillary is assumed to be governed by the Stokes equation. The fluid flow in the surrounding tissue is simplified as the Darcy flow. The advection–diffusion reaction equation is employed to investigate the NO distribution in a lumen-tissue model, which is originated from the endothelial cells inside the capillary wall. The characteristic Galerkin method is employed for the discretization of the advection-diffusion reaction equation. The simulated results show that the NO transport is effectively affected by different hydraulic permeabilities due to the changes of the blood velocity. When the hydraulic permeability increases considerably, the NO concentration ([NO]) in the whole domain decreases accordingly. Moreover, the NO concentration increases in the area after the bifurcation of the capillary owing to the convective effect. It is also shown that even if the NO production by the endothelial cells is enhanced, the increase of the convection inside the vessel may reduce the endothelial NO concentration. As a signal transduction molecule, the spatial location with discriminating NO distribution may be useful for determining the position of the microangiopathy in the DM.