In 24-month-old male Wistar rats, the endothelium-dependent (ED) and endothelium-independent (EI) responses of the arteries of the cranial pia mater (CPM) of branching orders I-V were studied by vital microscopy 30 days after the modeling of myocardial infarction. Sham-operated animals were used as a control. In both groups, a distinct response of the CPM vessels of different branching orders to vasodilators was observed: in pharmacological tests (acetylcholine, nitroglycerin), a dependence of the ED or EI vascular reactivity on the diameter of the arteries was found. In orders I-II branches, the myogenic ED response predominates, and the EI response of the vessels prevails in orders IV-V branches. In order III branches, both mechanisms were approximately equally developed. In most cases, the vascular reactivity and numerical density of arteries that changed their diameter were significantly lower in rats with myocardial infarction compared to control animals. Thus, in myocardial infarction, systemic disorders of the ED and EI reactivity of the CPM vessels of different diameters caused by endothelial dysfunction have been identified; the combination of these disorders with age-related changes determined rapid depletion of adaptive reserves and increased circulatory hypoxia in the brain. These processes lead to neurodegenerative changes, primarily in the oxygen-sensitive neurons of the frontal cortex, and to cognitive impairments.

The quantitative content of HIF-1α- and HIF-2α-immunopositive brain neurons in Wistar rats was studied 1, 15, and 30 days after modeling of myocardial infarction. In rats of the control group, the immunohistochemical markers HIF-1α and HIF-2α in the prefrontal cortex of the brain were determined in few pale-colored neurons and capillaries. One day after myocardial infarction simulation, the number of HIF-1α + neurons increased, and on day 15 it reached the maximum level: the concentration of immunopositive neurons and capillaries increased by 24.7 and 18.4%, respectively, in comparison with the control. After 30 days, the number of HIF-1α + structures decreased, but remained above the control values. The number of neurons and capillaries positively stained for HIF-2α peaked only on day 30 of the postinfarction period.

Biomicroscopy was used to study order I-IV branches of the uterine artery in sexually mature female Wistar rats after a single 5- or 10-min direct exposure of the right broad ligament of the uterus to a helium-neon laser beam in the red band of the spectrum (λ=632.8 nm, output power 2 mW, intensity 20 mW/cm2). Under the influence of laser exposure, there was a significant increase in the diameter of small uterine branches and a weaker increase in large vessels with a well-developed muscular membrane. Preliminary administration of zinc IX protoporphyrin hemoxygenase blocker (30 mmol/kg) reduced reactivity of the vascular bed to laser irradiation, mainly of order I-II branches. It was concluded that carbon monoxide can act as an intermediary between the laser exposure and uterine vessels.

Remembrance of the outstanding scientist Professor P.A. Motavkin is largely connected with the creation of the famous neuromorphological school in Vladivostok. During a relatively short historical period, scientific discoveries were made under the leadership of P.A. Motavkin. New ideas about the mechanisms of vascular regulation of the brain and spinal cord of humans and animals were presented on the basis of these discoveries. Extensive factual material accumulated over the years of research has allowed not only to identify the basic laws of the functioning of this regulatory system in normal conditions of life, but also to solve a number of problems related to the correction of its disorders in case of vascular diseases.

Using the biomicroscopy method, we studied the reaction of arterial and venous vessels of the broad ligament of the uterus in outbred female rats to irradiation with helium-neon laser (λ=632.8 nm; power output 2 mW). Small arteries were found to be most sensitive to laser irradiation. The veins of the broad ligament of the uterus demonstrated lower reactivity to laser irradiation of the same duration than arterial vessels, which can be explained by morphological, functional, and hemodynamic differences.

The results of modeling acute myocardial infarction on 20 male Wistar rats aged 24 months are presented. Ischemic effect is carried out by local injection of 1.5% sclerosant ethoxysclerol (0.25 ml) into the thickness of the myocardium under general anesthesia using non-traumatic needle with silicone coating, which allows to simulate acute myocardial infarction with minimal invasive effect on the animal's body, minimal trauma, little duration of intervention, low mortality, frequency of complications and absence of systemic action of drugs.

Cellular-molecular mechanisms and factors, regulating uterus vascularization are also a focal point ensuring reproduction processes. In the process of angiogenesis endothelium expresses a number of receptors of growth factors and ligands which control main stages of the cellular makeup during vascular walls formation process. It in turn supports proliferation and reparation of the endometrium during menstrual cycle and prepares for the implantation and placentation.

Cardiovascular diseases take a leading position in the structure of mortality in modern society. Most diseases are characterized by uncontrolled processes of oxidative stress, proteolysis, tissue and cellular hypoxia, which cause endothelial dysfunction. Tissue and cellular hypoxia accumulated with mitochondrial reactive forms of oxygen damaging lipoproteins, proteins, nucleic acids plays an important role in the pathogenesis of vascular aging. Cellular aging is characterized by a decrease in the number of mitochondria, a decrease in the number of copies of mitochondrial DNA, and the loss of mitochondrial protein. In addition to morphological changes, the function of mitochondria is oppressed, at the same time the activity of their proteins and enzymes decreases. Changes in the functions of mitochondria can be secondary in response to various stimuli and are associated with a violation of their structure and a change in activity in response to specific genetic and phenotypic conditions. Reprogramming of mitochondrial biogenesis occupies a central position in the theory of cellular aging and is one of the targets for interventions in prolonging active longevity.

Objective : The analysis of the antemortem changes of the microvasculature (MV) of the bulbar conjunctiva among older smokers. Methods: 42 smokers middle age (45–59 years old, n=10), old age (60–74 years old, n=12) and senile age (75–86 years old, n=14) were examined. Smoking history is from 21 to 26 years, the number of smoked cigarettes – from 14 to 18 pieces a day. Control: 28 nonsmokers of both genders 45–59 years old (n=7), 60–74 years old (n=11) and 75–86 years old (n=9). MV was studied applying bio microscopy method using non-hydriatic retinal camera TOPCON TRC-NW8F (Japan), linked to the measuring complex of the automatic system of image analysis ImageScope (Leica, Germany). Results : Arterioles spasm, unevenness of their caliber, the increase of the number of functioning anastomosis, disalignment of the microvessels and avascular fields were registered more frequently among older smokers, than among middle-aged smokers. Average arterioles diameter, arteriolar-venular coefficient (A/V) and specific density of capillaries were smaller, but the diameter of the venules was bigger among the older smokers than among nonsmokers of the corresponding age. The average arterioles diameter decreased by 22%, veins diameter increased by 15% among smokers aged 40–59. Both A/V coefficient and specific density of the capillaries reduced by 30 and 38% respectively. Among patients aged 60–74 the level of the relevant indicators declined by 5–8% on average. The differences of the examined parameters among smokers and non-smokers aged 75–86 were minimal and reached significant distinctions only on A/C coefficient and specific density of the capillaries. Conclusions : Chronic tobacco smoking has negative influence on MV of the bulbar conjunctiva among older people: average arterioles size, A/V coefficient and specific density of the capillaries reduces, but the average size of venules increases.

Structural organization of the microcirculatory bed and mast cells in the uterus of mature female Wistar rats ( n =60) were examined every 2 h over 24 h. During night hours, many vessels characterized by intensive reaction to NADPH-diaphorase and endothelial NO synthase were detected in the endometrium, and the density of these vessels and mast cells was quite high. During the day and evening hours, the capillaries with high levels of enzymes involved in NO synthesis and mast cells were less numerous. NO directly regulating the diameter of arteries and the intensity of transcapillary exchange can act as a signal molecule in the temporal dynamics of the vasoceptive action of estrogens and their receptors in the uterus.

Несмотря на то, что внутриорганное кровеносное русло является основным звеном для адекватного кровоснабжения органных структур, в матке ее строение, функции и механизмы регуляции во многом не изучены. В обзоре представлены данные литературы и собственные материалы по локализации и распределению газотрансмиттеров во внутриорганных сосудах матки. Рассматриваются клеточные и молекулярные механизмы участия NO, СО и HS в регуляции функций этих сосудов. Приведенные материалы, с одной стороны, подчеркивают значимость данных сигнальных молекул в регуляции сократимости гладких мышц сосудов, проницаемости капилляров, с другой - указывают на необходимость дальнейших исследований роли газотрансмиттеров в общей системе регуляции гемодинамики матки. Despite the fact that the intraorganic circulatory bed is the main element providing adequate blood supply to organ structures, its structure, functions and regulatory mechanisms in the uterus are largely unknown. The review presents the literature data and own materials on the localization and distribution of gasotransmitters in the intraorganic vessels of the uterus. The cellular and molecular mechanisms of the participation of NO, CO and H2S in the regulation of the function of these vessels are rewieved. On the one hand, these materials emphasize the importance of these signaling molecules in the regulation of contractility of the smooth muscles of the blood vessels and capillary permeability, on the other hand, point out the need for further studies of the role of gasotransmitters in the general system of uterine hemodynamic regulation.

Objective: Analysis of age-related changes of microcirculatory bed of bulbar conjunctiva.Methods: 46 individuals of both sexes, divided into 5 age groups according to WHO recommendations, were examined. Biomicroscopy of bulbar conjunctiva was performed using a non-mydriatic retinal camera TOPCON TRC-NW8F (Japan); the obtained images were processed with a mea‑ suring device of automated analysis system ImageScope (Leica, Germany).Results: The average diameter of arterioles, arterioleto-venule ratio (AVR) and specific density of capillaries were the largest, and the diameter of venules was the smallest among the subjects aged 18–44 years. The most sensitive indicators of the state of microcirculatory bed were AVR and the specific density of capillaries, the values of which in the group of 45–59-year-olds were 10–11% lower than in people aged 18–24 and 25–44 years. Differences in other indicators between people aged 18-24 and 45–59 years were not significant. Between the groups of 60–74 and 75–86-year-old participants of the study, pronounced differences (about 18%) were found only in the specific density of capillaries: compared with 18–24 and 45–59-year-olds, this indicator decreased by almost 1.5 times, AVR – only by a third, and changes in the average diameter of arterioles and venules did not exceed 9–12%. Elderly people more often demonstrated arteriolar spasm, their uneven caliber, avascular fields and other disorders of the structure of the micro‑ circulatory bed.Conclusions: As the body ages, in the microcirculatory bed of the bulbar conjunctiva, the number of atypical vascular formations increases, the diameter of the arterioles decreases, the AVR and the specific density of capillaries decrease, the diameter of the venules increases.

This review presents data on the cellular-molecular mechanisms regulating angiogenesis associated with the vascular endothelium. Existing concepts hold that the control of angiogenesis involves activated endothelial cells and their precursors (progenitor cells), which synthesize and release angiogenic molecules with different chemical structures and mechanisms of biological action, but all allowing these cells to control each stage of angiogenesis directly or indirectly. Balanced functioning of the system of molecular stimulators and inhibitors of angiogenesis is particularly important for the brain, as excessive formation of blood vessels, like inadequate development of blood vessels, leads in certain conditions to rapid and irreversible changes in nervous tissue. Post-operative neurorepair cannot occur without adequate reperfusion of the injured part of the brain, which can be supported by timely stimulation of angiogenesis, while intensification of this process in tumors, conversely, has adverse consequences. Tumor growth and metastasis are significantly linked with increases in the level of vascularization of malignant tissue, while blockade of angiogenesis is not infrequently the only productive method of limiting tumor growth. However, we have insufficient knowledge of the mechanisms regulating angiogenesis in the brain at the cellular-molecular level in physiological conditions and pathology, so angiogenic influences do not always produce the expected effect.

First to fourth-order branches of the uterine artery in sexually mature female Wistar rats were studied by biomicroscopy. After administration of a CO donor hemin (60 mM), the diameters of large uterine branches with a well-developed muscle layer markedly increased, while the increase in diameter of small vessels with one often interrupted layer of smooth muscle cells increased insignificantly. Zinc protoporphyrin IX (30 mM) in all cases blocked this effect. However, zinc protoporphyrin IX does not affect NO-mediated reaction of the branches of the uterine artery caused by administration of L-arginine (60 mM), and L-NAME did not significantly affect reactivity of uterine artery branches associated with the hemoxygenase-CO system. In contrast to NO, CO produced less potent and rapid, but more sustained effect. The target for the hemoxygenase-CO system is mainly arteries with developed muscular layer, while the target for the NO synthase-NO is small vessels where endothelium plays a Rdecisive role in the regulation of vasomotor reactions.

AIM:To obtain the data on the spatial relationships between catecholamine (TH-positive) and nitroxidergic (nNOS-positive) neurons in vasomotor nuclei of the medulla in different periods of hypertension development.MATERIAL AND METHODS:The experiment was performed on male Wistar rats (n=45) with induced renovascular hypertension (RVH). TH and nNOS in neurons of solitary tract nuclei, reticular small-and giant cell nuclei were detected using immunohistochemical methods.RESULTS AND CONCLUSION:The most early and severe changes in the intensity of reaction and amount of nNOS-positive neurons were noted in the solitary tract nucleus. Significant changes in the quantitative parameters of TH-positive neurons in RVH were identified only in the reticular giant cell nucleus but they appeared later and were less expressed compared to nNOS-positive cells. This resulted in the changes of spatial relationships between two types of neurons and remodeling of the bulbar region of the cardiovascular center.

The review analyzes literature data and authors' materials on organization of uterus microvasculature and its regulatory mechanisms. It justifies the hypothesis that the adaptation of the microcirculatory system of the uterus to the changing conditions of the organ functioning is provided by regulatory mechanisms acting indirectly, by changing the lumen of the inflow and outflow vessels, or directly through the structural elements of the vessel wall, mainly the endothelium. It discusses the role of gasotransmitters in this process: nitric oxide, Обсуждается роль в этом процессе газотрансмиттеров: оксида азота, carbon monooxide, hydrogen sulfide.

We measured the content of HIF-1α and HIF-2α-immunopositive neurons and microvessels in the brain of Wistar rats during the first 24 h of tissue hypoxia induced by subcutaneous injection of cobalt dichloride (50 mg/kg). In control rats (without hypoxia), immunohistochemical marker HIF-2α in cortex of parietal lobe was not detected, and HIF-1α was detected only in few weakly stained pale neurons and capillaries. In 30 min after injection of the cobalt salt, the number of HIF-1α+ neurons increased by 25.6% (in capillaries by 12.3%), many of these were characterized by intensive reaction; the quantitative parameters reached their maximum level within 1-3 h. However, the concentration of immunopositive neurons returned to the control values in 6 h after hypoxia modeling (capillaries in 9 h). In contrast to HIF-1α, the number of neurons and capillaries containing HIF-2α reached a maximum level in 6-12 h of hypoxia. The relative density of HIF-2α+ capillaries increased most pronouncedly (by 23.6%); the relative density of neurons increased by 18.9%. The relative density of HIF-2α+ cells did not change significantly to the end of the experiment. Thus, HIF-1α is more essential for regulation of adaptation to hypoxia in neurons and HIF-2α is more important for the endothelium of microvessels.

AIM To study the distribution of MMP-2 and MMP-9 and their inhibitors (TIMP-2 and TIMP-1 respectively) in the brain vascular bed of rats exposed to chronic tobacco smoke. MATERIAL AND METHODS Localization and expression of MMP-2, MMP-9, TIMP-2 and TIMP-1 in the pial branches (I-V order vessels), intracerebral arteries and capillaries of rats exposed to tobacco smoke were studied for 36 weeks. The level of enzymatic activity was assessed by the relative quantity of enzymopositive arteries and amount of fragments per 1 mm2 and rate of immunohistochemical reaction. Specific capillary density per mm2 of brain tissue and optical density of the immunohistochemical product were calculated. RESULTS MMP-2 and TIMP-2 were found in all segments of the arterial course in control animals. In rats exposed to tobacco smoking, the expression of MMP-2 increased only in intracerebral arteries and capillaries while TIMP-2 level decreased. MMP-9 and TIMP-1 were noted only in single vessels, mainly small pial and intracerebral arteries, in intact animals. In rats exposed to tobacco smoke, MMP-9 expression significantly increased in all segments of the arterial course whereas the increase in TIMP-1 was observed mainly in large pial arteries. CONCLUSION In physiological conditions, the dynamic balance between MMP-2 and TIMP-2 maintains basic tissue metabolism. Products of tobacco combustion are inductors of the inducible MMP-9 which promotes morphofunctional changes. The imbalance in MMP-9 - TIMP-1 system causes the degradation of extracellular matrix in different segments of the brain arterial course promoting the development of cerebral dysfunction.

The locations of heme oxygenase-2 (HO-2) and heme oxygenase-1 (HO-1) in the walls of 1st- to 4th-order arterial branches in the pia mater were studied in normotensive rats and in animals with induced renovascular hypertension (RVH). Immunohistochemical detection of heme oxygenase was performed on 40 Wistar rats. The vasomotor function of carbon monoxide (CO) in 3rd- to 5th-order arteries was found to be associated mainly with the endothelium, while in 1st- and 2nd-order arteries it was associated with myocytes. In normotensive animals, HO-2 was involved in forming CO, while both HO-2 and HO-1 had roles in hypertensive animals. The largest number of vessels expressing HO-1 was seen in week 16 of RVH, when the proportion of vessels positive for HO-2 was minimal, which is consistent with the time at which arterial pressure stabilizes at the new, higher, level.