THE GRADIENT OF VASCULAR PERMEABILITY : III. THE GRADIENT ALONG THE CAPILLARIES AND VENULES OF FROG SKIN

A steeply mounting gradient of permeability is demonstrable along the meshwork of capillaries which connects the arterioles and venules of the skin of the frog. The venules incorporated in the meshwork are even more permeable than the capillary meshes giving into them. The presence of the gradient under such differing conditions as exist along frog and mammalian capillaries enables one to rule out certain factors which might be invoked to explain it; and it is not explainable in terms of those influences generally recognized as conditioning exchange between the blood and tissues. Not improbably it results from a structural differentiation along the capillary.     

THE VESSELS INVOLVED IN HYDROSTATIC TRANSUDATION

The gradient of permeability which exists along the cutaneous capillaries and venules is accentuated and broadened in scope by increasing the venous pressure moderately. Under such circumstances transudation leading to edema takes place most abundantly from the venules. The permeability of the portion of the capillary web that is near the arterioles increases only when the venous pressure rises so high as to approximate that in the arteries. Under such circumstances the gradient of permeability along the small vessels disappears, the capillaries and venules everywhere leaking fluid. The character of the vital staining developing under such circumstances indicates, like the evidence of previous work, that the cause for the gradient is to be sought in a structural differentiation.     

THE EFFECTS OF RENAL HYPERTENSION ON THE VESSELS OF THE EARS OF RABBITS

1. The present experiments demonstrate by direct observation that peripheral arterioles in moat chambers in rabbits'' ears constrict during the development of renal hypertension, and that they remain persistently constricted, although not sufficiently to interrupt the blood supply to the tissues. The arteriolar constriction in the hypertensive animals was not dependent upon nerves, since it occurred in newly formed arterioles which had probably never been supplied with nerves, as well as in older arterioles with a functional nerve supply. 2. No capillary constriction was observed during or following the development of hypertension, although the walls of the capillaries could be very clearly seen. Persistent hypertension was associated in two examples with increased sticking of leukocytes to the walls of the capillaries and venules, some emigration of leukocytes, and a few small hemorrhages. 3. During development of hypertension, new arteriovenous anastomoses were observed to appear in the chambers. 4. No evidence of change was noted in the viscosity of the blood or in the appearance of the blood corpuscles in the hypertensive rabbits. 5. The constriction of the arterioles during and following the development of hypertension closely resembled that produced by intravenous injections of angiotonin.     

Expression of the vascular endothelial growth factor (VEGF) family in human endometrial blood vessels

Endometrial regrowth is associated with intense angiogenesis, for which vascular endothelial growth factor-A (VEGF-A) is an important regulator. However, the expression of other members of the VEGF family is less well documented. The aim of this study was to localize members of the VEGF family (VEGF-A,-B and-C), and their receptors (VEGFR1, 2 and 3) in human endometrial blood vessels. Endometrial biopsies collected from four healthy and fertile women were used for immunohistochemistry assessments. Co-localization of VEGF-family proteins with CD34 stained endothelial structures was determined by image analysis. We demonstrate here the marked expression of VEGF-A as well as VEGFR2 and 3 in capillaries. Arterioles expressed VEGF-B, VEGFR1, 2, and 3 moderately and VEGF-A variably. Venules expressed only VEGFR3 markedly. In contrast, VEGF-C was not expressed in the arterioles, but moderately in the capillaries and weakly in the venules. VEGF-B was expressed in all blood vessels; however, VEGF-B was weakly expressed in capillaries and arterioles and moderately expressed in venules and arterioles. Thus, expression of VEGF-A, B and C and VEGF receptors 1-3 in endometrial blood vessels indicates a highly structured involvement of VEGF in the regulation of angiogenesis in the human endometrium.     

Subpleural microvascular flow velocities and shear rates in normal and septic mechanically ventilated rats

Changes in pulmonary microhemodynamics are important variables in a large variety of pathological processes. We used in vivo fluorescent videomicroscopy of the subpleural microvasculature in mechanically ventilated rats to directly monitor microvascular flow velocity (FV) and shear rate in pulmonary arterioles, capillaries, and venules in healthy rats and in septic rats 20 h after cecal ligation and puncture (CLP). Observations were made through a small thoracotomy after injection of fluorescent microspheres (D = 1 microm) into the systemic circulation. The FVs were calculated off-line by frame-by-frame measurements of the distance covered by individual microspheres per unit of time. In healthy rats, inspiratory FV were 1322 +/- 142 microm/s in subpleural arterioles and 599 +/- 25 microm/s in capillaries. The highest FV was found in venules (1552 +/- 132 microm/s). The calculated shear rates were 547 +/- 62/s in arterioles and 619 +/- 19/s in capillaries. The highest shear rates were detected in venules (677 +/- 59/s). No significant changes in FV and shear rates were observed throughout the 1-h observation period in any of the microvascular compartments. Pulmonary microvascular FV and shear rates found in sham-operated rats in the CLP experiments were not significantly different from values of healthy rats. The CLP caused a significant increase in leukocyte sequestration in the lungs and a mean of 27% to 34% decrease in FV in all sections of the pulmonary microvasculature (P < 0.001 in capillaries and P < 0.05 in venules). Also, CLP caused a 23% decrease in capillary shear rate that reached only borderline statistical significance (P < 0.06) and a significant 35% decrease in mean shear rate in venules (P < 0.05). Fluorescent videomicroscopy is offered as a stable and reproducible method for in vivo determinations of pulmonary microhemodynamics in clinically relevant models of sepsis.     

Expression of the vascular endothelial growth factor (VEGF) family in human endometrial blood vessels

Endometrial regrowth is associated with intense angiogenesis, for which vascular endothelial growth factor-A (VEGF-A) is an important regulator. However, the expression of other members of the VEGF family is less well documented. The aim of this study was to localize members of the VEGF family (VEGF-A, -B and -C), and their receptors (VEGFR1, 2 and 3) in human endometrial blood vessels. Endometrial biopsies collected from four healthy and fertile women were used for immunohistochemistry assessments. Co-localization of VEGF-family proteins with CD34 stained endothelial structures was determined by image analysis. We demonstrate here the marked expression of VEGF-A as well as VEGFR2 and 3 in capillaries. Arterioles expressed VEGF-B, VEGFR1, 2, and 3 moderately and VEGF-A variably. Venules expressed only VEGFR3 markedly. In contrast, VEGF-C was not expressed in the arterioles, but moderately in the capillaries and weakly in the venules. VEGF-B was expressed in all blood vessels; however, VEGF-B was weakly expressed in capillaries and arterioles and moderately expressed in venules and arterioles. Thus, expression of VEGF-A. B and C and VEGF receptors 1-3 in endometrial blood vessels indicates a highly structured involvement of VEGF in the regulation of angiogenesis in the human endometrium.     

Die Beeinflussung des in situ gemessenen extravasalen Proteingehaltes durch Änderung der Gefäßpermeabilität

The extravascular protein contents in the perivascular connective tissue of a rat's mesenterial plate was measured ultramicrospectrophotometrically in situ and in vivo after changing the hydrostatic and colloidosmotic pressures of the blood. We analized the perivascular area of the different microcirculatory vessels, arterioles, capillaries and venules. The perivascular protein contents, which corresponds besides arterioles to 40% and besides venules to 59% in comparison to the intravascular blood plasma, decreased in a comparison group under the osmotic influence of the perfusion liquid on the mesenterial plate. An injection of an isotonic saline solution is followed only by small fluctuations of the perivascular protein contents during one hour. After blood loss a transitional increase of extravascular protein at the perivenular area was observed indicating the mobilisation of protein depots. Around arterioles the extravascular protein contents did not change significantly. An intravenous injection of albumin solution was followed by a short-termed increase of tissue protein around the arterioles. Around the venules after 50 minutes the extravascular protein contents increased significantly. Within one hour after the changes of the permeability conditions the maximal induceable protein movements in the perivascular space were calculated as +/- 1.35 g% plasma protein concentration corresponding to a maximun protein exchange of +/- 3.1 mg ml(-1) tissue.     

比较脂质微泡与聚合物超声造影剂的微循环流变学

目的 探讨脂质微泡与高分子聚合物超声造影剂在大鼠肠系膜微循环中的流变学特征。方法 对10只大鼠经股静脉分别注射DiI标记的脂质微泡和高分子聚合物超声造影剂,通过倒置荧光显微镜观察两种不同造影剂在大鼠肠系膜微循环中的运动情况;比较注射前后小动脉、小静脉及毛细血管内径的变化,测定红细胞与两种造影剂在微循环内的流速。结果 注射后两种造影剂在大鼠肠系膜微循环内均可随血流移动,仅见少量脂质微泡短暂滞留。注射造影剂前后小动脉、小静脉及毛细血管内径无明显改变(P>0.05);两种造影剂在微循环内的流速与红细胞相似,差异无统计学意义(P>0.05)。结论 脂质微泡和高分子聚合物超声造影剂具有与红细胞相似的微循环流变学特征,均可作为红细胞示踪剂。     

THE STATE OF THE VESSELS OF THE MESENTERY IN SHOCK PRODUCED BY CONSTRICTING THE LIMBS AND THE BEHAVIOR OF THE VESSELS FOLLOWING HEMORRHAGE

1. Direct observations of the arteries, arterioles, capillaries, veins, and lymphatics in the mesentery of anesthetized cats put into shock by incomplete occlusion of the circulation of the limbs showed that: (a) Marked constriction of the arteries and arterioles, produced by muscular contraction, occurred usually within an hour after incomplete occlusion of the limbs, lasted several hours, and finally gave way in most instances to relaxation an hour or more before death. The constriction reduced the blood supply to the mesentery and intestine and the venous return from them. It did not, however, interrupt the blood flow. No pooling or stagnation of blood was seen even as a terminal phenomenon. (b) The veins of the mesentery also became constricted but showed less tendency to dilate as death approached. The lymphatics likewise became somewhat narrowed. Even during the terminal stage the leukocytes moved along without change in shape or sticking to the walls of the capillaries or venules. (c) Hematocrit determinations showed progressive hemoconcentration of moderate degree. (d) Autopsy usually showed the presence of small hemorrhages in many parts of the body, especially the heart, liver, spleen, and lungs. (e) Bilateral nephrectomy, suprarenalectomy, and pancreatectomy did not significantly alter the morphological picture elicited by shock induced by restriction of the circulation to the limbs. 2. Removal of large amounts of blood was always followed within a short time by constriction of arteries, arterioles, veins, and lymphatics of the mesentery. 3. Fall in arterial pressure produced by pithing was not accompanied by change in diameter of the arteries, arterioles, veins, or lymphatics, or by blanching of the mesentery or gut.     

Microvascular rheology of Definity microbubbles after intra-arterial and intravenous administration.

The microvascular rheology and extent of pulmonary retention of second-generation microbubble ultrasound contrast agents has not previously been well characterized. We assessed the microvascular behavior of Definity, a lipid-shelled microbubble agent containing perfluoropropane gas, using intravital microscopy of either rat spinotrapezius muscle or mouse cremaster muscle. Immediately after intra-arterial injection, which was performed to model pulmonary retention, larger microbubbles (> 5 microm) were entrapped within small arterioles and capillaries. The retention fraction of microbubbles was low (1.2% +/- 0.1%) and entrapment was transient (85% dislodged by 10 minutes), resulting in no adverse hemodynamic effects. Leukocyte or platelet adhesion at the site of entrapment was not seen. After intravenous injection, no microbubble entrapment was observed and the velocities of microbubbles in arterioles, venules, and capillaries correlated well with those of red blood cells. We conclude that after intravenous injection and pulmonary passage, the microvascular rheology of Definity microbubbles is similar to that of red blood cells. Microbubble entrapment within the pulmonary microcirculation after venous injection should be negligible and transient. These findings are important for establishing the safety of this agent.     

Brain arterioles show more active vesicular transport of blood-borne tracer molecules than capillaries and venules after focused ultrasound-evoked opening of the blood-brain barrier

Previously, activation of vesicular transport in the brain microvasculature was shown to be one of the mechanisms of focused ultrasound-induced blood-brain barrier (BBB) opening. In the present study, we aimed to estimate the rate of the transendothelial vesicular traffic after focused ultrasound sonication in the rabbit brain, using ultrastructural morphometry and horseradish peroxidase (HRP) as a tracer. In the capillaries, the mean endothelial pinocytotic densities (the number of HRP-containing vesicles per microm(2) of the cell cytoplasm) were 0.9 and 1.05 vesicles/microm(2) 1 h after sonication with ultrasound frequencies of 0.69 and 0.26 MHz, respectively. In the arterioles, these densities were 1.63 and 2.43 vesicles/microm(2), values 1.8 and 2.3 times higher. In control locations, the densities were 0.7 and 0.14 vesicles/microm(2) for capillaries and arterioles, respectively. A small number of HRP-positive vesicles were observed in the venules. Focal delivery of HRP tracer was also observed in light microscopy. The results indicate that the precapillary microvessels play an important role in macromolecular transcytoplasmic traffic through the ultrasound-induced BBB modulation, which should be considered in the future development of trans-BBB drug delivery strategies.     

Changes in the cardiac hemodynamics and coronary blood flow in acute myocardial infarction due to perftoran

One hundred and twenty patients with acute myocardium infarction, who were receiving perftoran, were analyzed within the case study. The microcirculation condition was determined by biomicroscopy of the eye conjunctiva capillaries. Changes in capillaries were evaluated by the Ditzel classification. Hemostasis was evaluated by coalugram. The condition of the myocardium was examined by electrocardiography and Echo-cardiography. The contractive ability of the myocardium was assessed by a shortening degree of the anterior-posterior size and by the ejection fraction. According to the study results, the administration of perftoran increased the number of functioning capillaries, decreased the venous congestion and reduced the diameter of arterioles and venules. Hypercoagulation was significantly decreasing. The general evaluation of the contractive ability of myocardium was satisfactory in all patients.     

Role of CD11/CD18 in shear rate-dependent leukocyte-endothelial cell interactions in cat mesenteric venules.

In vivo microscopy was used to assess the relationships among shear rate (and shear stress), leukocyte rolling velocity, and leukocyte adherence in a cat mesentery preparation. Shear rate in individual venules and arterioles of 25-35 microns diameter were varied over a wide range by graded occlusion of an arterial loop. There was a linear decline in leukocyte rolling velocity (Vwbc) as red cell velocity (Vrbc) was reduced. The ratio Vwbc/Vrbc remained constant despite variations in shear stress from 5-25 dyn/cm2. A reduction in shear stress was associated with an increased leukocyte adherence, particularly when Vwbc was reduced below 50 microns/s. Reduction in wall shear rate below 500 s-1 in arterioles allowed 1-3 leukocytes to adhere per 100 microns length of vessel, while venules exposed to the same shear rates had 5-16 adherent leukocytes. In arterioles, leukocyte rolling was only observed at low shear rates. At shear rates less than 250 s-1 leukocyte rolling velocity was faster in arterioles than venules, and the ratio Vwbc/Vrbc for arterioles was 0.08 +/- 0.02, which was fourfold higher than the ratio obtained in venules at similar shear rates. Pretreatment with the CD18-specific antibody (mAb) IB4 increased leukocyte rolling velocity in venules by approximately 20 microns/s at red cell velocities below 2,000 microns/s. mAb IB4 largely prevented the leukocyte adherence to arterioles and venules, and increased the ratio Vwbc/Vrbc observed in venules at low shear elicit a CD18-dependent adhesive interaction between leukocytes and microvascular endothelium, and that differences in shear rates cannot explain the greater propensity for leukocyte rolling and adhesion in venules than arterioles.     

THE EFFECT OF MULTIPLE EMBOLI OF THE CAPILLARIES AND ARTERIOLES OF ONE LUNG

1. Injection of a suspension of potato starch cells into the left branch of the pulmonary artery, in quantity sufficient ordinarily to give rise to markedly accelerated respirations, resulted in no change in respiratory rate. 2. A method for injecting substances into the pulmonary artery or its branches without interfering with the blood flow to the lungs has been described. 3. Injection of similar material into one lung when the other is excluded from the circulation either by ligation or by temporary clamping does give rise to rapid and shallow breathing (from a rate of 10 to 15 per minute to one of 60 or over) identical in character to that brought about by introducing emboli into both lungs. 4. A method for clamping and releasing the pulmonary artery or its branches in a dog breathing normally with closed thorax has been devised. This is described in detail in another paper. 5. After rapid breathing has been initiated by the effect of emboli lodged in the arterioles and capillaries of the right lung, reestablishing the circulation in the other lung by releasing the clamp on its artery may or may not restore the respiratory rate to its original, normal level. 6. This discrepancy in results has not been correlated with any difference in oxygen saturation of the arterial blood, or in carbon dioxide tension or pH of its plasma. 7. It is, however, believed to be related to the gross and microscopic anatomy of the lung of which the artery has been temporarily clamped. Photomicrographs are published, showing in one dog (No. 3), in which the respiratory rate returned to normal, a normal histological picture of the left lung, and in another dog (No. 4), in which the rate remained rapid after release of the clamp, a picture characterized by congestion and dilatation of arterioles and capillaries. 8. The fact that accelerated respirations result from emboli in the pulmonary capillaries and arterioles only after a certain quantity of material has been introduced, and the fact that emboli in one lung do not occasion accelerated respirations unless the circulation through the other lung is occluded or abnormal, leads us to the conclusion that the phenomenon is not an irritative stimulus due to foreign bodies, but is in some manner related to (a) diminution of the pulmonary vascular bed, (b) resistance to the blood flow through the lungs or (c) congestion or dilatation of the arterioles and capillaries of the lungs.     

Polyarteritis nodosa complicated by antiphospholipid syndrome

Polyarteritis nodosa is a necrotizing vasculitis of small and medium-sized arteries that spares the smallest blood vessels (arterioles, venules, and capillaries). Antiphospholipid syndrome is an autoimmune disorder characterized by venous or arterial thrombosis and/or by fetal losses, associated with antiphospholipid antibodies. The association of both diseases is infrequent. This case report discusses a male patient with a diagnosis of polyarteritis nodosa who, after 7 years of being diagnosed with vasculitis, showed ischemic lesions in his legs associated with high titers of anticardiolipin antibodies, along with angiographic and histologic evidence of thrombosis. Despite immunosuppressive and anticoagulant therapy, his lesions progressed, and both legs had to be amputated.     

THE GRADIENT OF VASCULAR PERMEABILITY

The permeability of the capillaries in the skeletal muscles of mammals increases progressively along their course and is greatest where they pass into the least venules. The gradient of permeability is so largely independent of functional states as to give grounds for the view that it is determined by inherent local differences. Through the gradient opportunity is equalized along the capillary. In the liver lobule this object is accomplished by an artifice of arrangement whereby the blood flow past the cells is increased with their distance from the source of supply. In the urinary bladder the interlacing of capillaries, their progressive widening, and a consequent gradual slowing of the blood flow act to achieve the same end. Here a gradient of permeability has not been demonstrable. Where cells of different sorts are served by a slender capillary, their differing requirements may render unnecessary any provision to equalize their opportunities; but where shortcomings in local maintenance will reduce the efficiency of an entire fabric, as the muscle fibre, and where cells of like character live competitively along the same channel, as in the liver, some arrangement must exist to ensure an even distribution of the services rendered by the blood. In situations of the kind last mentioned the immediate environment of the individual cell, the "milieu interne" of Bernard, is not only kept as constant as possible but it must be the same, by and large, for all of the cells. The task of serving voluntary muscle is not strictly limited to the capillaries. The intrafascicular arterioles and venules act so effectively to sustain the tissue about them that where they run no capillaries are supplied.     

EVIDENCE FOR A BLOOD-THYMUS BARRIER USING ELECTRON-OPAQUE TRACERS

In order to verify the existence of a blood-thymus barrier to circulating macromolecules, the permeability of the vessels of the thymus was analyzed in young adult mice using electron opaque tracers of different molecular dimensions (horseradish peroxidase, cytochrome c, catalase, ferritin, colloidal lanthanum). Results show that although blood-borne macromolecules do penetrate the thymus, their parenchyma] distribution is limited to the medulla of the lobe by several factors: (a) the differential permeability of the various segments of the vascular tree; (b) the spatial segregation of these segments within the lobe; (c) the strategic location of parenchymal macrophages along the vessels. The cortex is exclusively supplied by capillaries, which have impermeable endothelial junctions. Although a small amount of tracer is transported by plasmalemmal vesicles through the capillary endothelium, this tracer is promptly sequestrated by macrophages stretched out in a continuous row along the cortical capillaries and it does not reach the intercellular clefts between cortical lymphocytes and reticular cells. The medulla contains all the leaky vessels, namely postcapillary venules and arterioles. Across the walls of the venules, large quantities of all injected tracers escape through the clefts between migrating lymphocytes and endothelial cells; also the arterioles have a small number of endothelial junctions which are permeable to peroxidase, but do not allow passage of tracers of higher molecular weight. The tracers released by the leaky vessels penetrate the intercellular clefts of the medulla, but they never reach the cortical parenchyma, even at long time intervals after the injection. Therefore, a blood-thymus barrier to circulating macromolecules does exist, but is limited to the cortex. Medullary lymphocytes are freely exposed to blood-borne substances.     

Orientation of microvascular blood flow in pancreatic islet isografts.

There is evidence that intraislet cellular communication and hormone delivery within the islets of Langerhans is controlled via capillary perfusion directed from the B cell core to the A/D cell mantle (intraislet portal system). To determine whether vascularization of freely transplanted islets repeats this "core-to-mantle" capillary perfusion, hamster islets were isolated by collagenase digestion and transplanted into a skinfold chamber of syngeneic animals (n = 12). 14 d after transplantation, the microvasculature of the islet grafts was analyzed by in vivo fluorescence microscopy. The capillary glomerulum-like network of the islet grafts (n = 109) was found supplied by individual arterioles, which regularly pierced the islet and broke into capillaries within the graft (96/109 [88.1%]), resulting in capillary flow directed from the core to the islet's periphery. Only in 13 of 109 islets (11.9%) arterioles broke into capillaries at the outside margin of the islet and capillary flow was directed simultaneously to vessels located within the core, as well as the periphery of the graft. The islet's capillary network was drained by individual venules and intercapillary anastomoses between the newly formed islet capillaries and the preexisting capillaries of the host muscle tissue. Immunohistochemical staining revealed B cells located within the core, and A and D cells scattered in the periphery of the islets, indicating reestablishment of sequential B-->A/D cellular perfusion of the grafts. Thus, freely transplanted islets develop an intra-islet portal system, similarly to that of pancreatic islets in situ.     

Microvascular dysfunction and skeletal muscle oxygenation assessed by phase-modulation near-infrared spectroscopy in patients with septic shock

Objective Sepsis is now considered a disease of the microcirculation. Little is known about the various sepsis-induced changes responsible for microvascular dysfunction. We investigated human microvascular function, regulation, oxygenation, and cellular metabolism during subacute septic shock.Design and setting Prospective case-control study in a nine-bed polyvalent surgical ICU of a university hospital.Patients and participants A prospectively enrolled group of 26 patients (13 with septic shock, 13 nonseptic postsurgical patients) and 15 healthy volunteer controls.Measurements and results The absolute tissue hemoglobin concentrations (oxygenated hemoglobin and deoxyhemoglobin) were measured noninvasively in arterioles, capillaries, and venules by phase-modulation near-infrared spectroscopy in the human brachioradial muscle during a series of venous occlusions and an arterial occlusion (ischemia) induced by applying a pneumatic cuff. These measurements were used to calculate tissue blood volume, postischemic hemoglobin resaturation time, microvascular compliance, and O₂ consumption. Patients with sepsis had significantly higher tissue blood volume values and lower compliance than healthy controls. They also had longer postischemic hemoglobin resaturation times than the other two groups and blunted resaturation curves. O₂ consumption was lower in patients with sepsis than in healthy controls. In patients with septic shock cuff-induced ischemia left O₂ consumption unchanged, whereas in healthy volunteers it reduced O₂ consumption to values almost matching those of patients with septic shock.Conclusions These findings show that septic shock alters microvascular muscle function and regulation. Diminished local VO₂ presumably reflects maldistribution and faulty autoregulation of local blood flow.     

The pericytes, endothelium monolayer, collagen and elastin chains as the elements of areolar tissue and the substrates of chemical reaction of glyserization

The microangiopathy under hyperglycemia and diabetes develops only in the microcirculation component of circulatory system. In this area considerable amount of pericytes is concentrated. These cells contain myofibrils and in circulatory mode envelop capillaries being situated on the outside of basilemma. It is possible that in a phylogenetic sense this is the earliest functional unity of endothelium monolayer as a pacemaker and pericytes as contractile elements which are the earliest "propeller" because of implementing the function of advancement of lymph, hemolymph and blood in capillaries. Probably, endothelium and pericytes formed the first variation of peristaltic "pump" for the purpose of blood advancement longwise of capillaries. Most probably, the state of distal part of arterial race (muscular type arterioles) impact the parameters of proximal part of arterial race (elastic type arterioles) and myocardium itself in the same extent as the state of "pump" in capillaries, endothelium and pericytes function impact the function of local peristaltic pumps (muscular type arterioles) in paracrine cenosis. It is supposed that the pericytes are the regulators of physical, hydraulic factor of activation of biologic reaction of transcitosis--excretion of nutrients and humoral mediators from capillaries to the pool of intercellular medium to perform the biologic function of homeostasis. Hyperglycemia, glycotoxins formation, bivalent substances (glyoxal, methilglyoxal, malonic dialdehyde) reacting simultaneously by both ends of molecule result in formation within collagen of areolar tissue of short transversal cross-links (glycosylation end product) which significantly increase rigidity (hardness) of capillary wall. In these conditions, myofibrils of pericytes no longer form directed deformation of capillary wall to effect peristalsis and advancement of hemolymph (blood later on) along capillaries according the synthesis of monolayer endothelium NO as a dilatation factor. This is the cause of blood circulation disturbance on the level of exchange capillaries and formation of chronic hypoxemia resulting in the only increase of rate of glycosylation chemical reaction. The microangiopathy is formed in the cells and tissues in an integrated pool of intercellular medium and never occurs in the cerebrospinal fluid pool where no hyperglycemia develops.