Russian Journal of Physiology

Angiogenesis is the formation of blood vessels from existing vasculature to provide n-ormal tissue perfusion. Angiogenesis is also necessary for the processes of growth and regeneration. Angiogenesis attracts the attention of researchers from the position of its therapeutic regulation: enhancement can contribute to significant progress in the treatment of ischemic diseases, and inhibition is actively studied for the treatment of neoplastic diseases. Regulation of angiogenesis is impossible without accurate knowledge of its mechanism. There are two fundamental pathways for angiogenesis: sprouting angiogenesis, which is mediated by an existing vessel’s endothelial cells migration into the extracellular matrix to form a vessel in the direction of angiogenic stimuli, and intussusceptive angiogenesis, which is mediated by dividing the formed vessel into two new ones as a re-sult of the formation of a partition inside it that separates two independent lumens. This review examines the main stages of each type of physiological angiogenesis, their mechanisms and regulation.

According to modern concepts, the composition and diversity of the intestinal microbiota play an essential role in maintaining immunity, homeostasis, and, in general, the physiological functions of the host organism. Recently the positive role of the microbiota and its metabolites especially short-chain fatty acids, in the metabolism and functional activity of skeletal muscles was reported. The aim of our work was to analyze muscle strength and motor coordination in mice after injection of broad–spectrum antibiotics with simultaneous administration of a microbiota metabolite – one of the representatives of short-chain fatty acids – butyric acid. In addition, we determined the level of malondialdehyde, the concentration of total glutathione and the activity of glutathione peroxidases in the muscles of the hind limbs in mice with administration of antibiotics and butyric acid. The administration of antibiotics to adolescent mice for two weeks induced higher mortality and decrease of weight, and also caused significant changes in motor behavior, including an increase in horizontal motor activity, decrease in vertical motor activity, muscle strength, and motor coordination. A higher level of oxidative stress was found in the muscle tissues of the hind limbs of mice treated with antibiotics. At the same time, oral administration of butyric acid prevented the observed changes and improved not only behavioral disorders, but also partially reduced the level of oxidative stress. In conclusion, metabolite of normal microbiota has a positive effect on the functional and biochemical parameters of skeletal muscles in dysbiosis, which can be used to prevent loss of muscle function in various pathological conditions.

The aim of this study was to evaluate the vasoactive and neuroprotective effects of c-Jun-N-terminal kinase inhibitor IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) in chronic cerebral hypoperfusion caused by irreversible bilateral ligation of carotid arteries. Cerebral blood flow was measured quantitatively (hydrogen clearance method) simultaneously in the parietal cortex, hippocampus, substantia nigra, and striatum of the brain of awake rats. It was found that ligation of the carotid arteries caused a decrease in blood flow in the brain structures with a more pronounced decrease in the cortex (by 48% of the initial level) and with the smallest drop in the substantia nigra (by 25% of the initial level). The reduced level of blood flow persisted for 14 days of measurements. The responses of the cerebral vessels to hypercapnic probes (5% CO₂) were lost during the 2-week hypoperfusion period, and the neurological status of the animals did not improve. The administration of IQ-1 (50 mg/kg, intraperitoneally, every 48 hours for 14 days) was accompanied by an increase in blood flow in all brain structures. The maximum increase in blood flow was observed in the striatum and the minimum in the substantia nigra. After the administration of IQ-1, the sensitivity of the cerebral vessels to the hypercapnic stimulus was restored and the neurological state of the animals significantly improved by the end of the second week of cerebral hypoperfusion. The results show that the use of the JNK inhibitor can reduce cerebrovascular disorders and associated neurological disorders in hypoperfusion brain injury.

Excessive salt intake is accompanied by the development of cardiovascular disorders, not always associated with an increase in blood pressure (BP). Given the cardioprotective effect of soy proteins in chronic kidney disease, the question arose of the possibility of leveling dietary interventions, in particular soy proteins, the damaging effect of a high-salt diet on the cardiovascular system. The aim of this work is to study the effect of long-term use of a diet high in NaCl and soy protein on myocardial remodeling and skin histomorphology in monkeys. The study was performed on male Javan macaques (Macaca fascicularis). The control group received a standard diet (2 g NaCl/kg feed). The second was a high-salt diet (8 g NaCl/kg feed), the third was a high-salt diet and SUPRO760 soy protein (200 g/kg feed). Echocardiography, registration of BP and heart rate were performed at baseline, after 4 and 12 months. After 12 months, a histological examination of the musculocutaneous flap was performed. In all animals, BP and heart rate did not change significantly during 12 months. In macaques on a high-salt diet, by the end of the study, deterioration in systolic and diastolic functions of the left ventricle (LV) was noted. In animals receiving additional soy protein, these changes leveled out. After 12 months, macaques fed soy protein had LV myocardial mass smaller and higher LV contractility than animals fed excess salt without soy protein. In monkeys on a high-salt diet, accumulation of collagen fibers in the hypodermis, hyalinization of the cytoplasm of capillary smooth muscle cells, perivascular and perineural edema of the reticular dermis were revealed. In animals treated with soy protein, skin capillary remodeling was less pronounced. Thus, high salt intake leads to adverse structural and functional disorders of the heart and blood vessels in cynomolgus monkeys, not associated with an increase in blood pressure. The inclusion of soy isolate in the diet reduces the negative effects of a high-salt diet on the cardiovascular system.

Decerebrated animals are often used in experimental neurophysiology to study multilevel physiological processes. The model of a decerebrated cat is traditionally used to study locomotion in acute experiments. We wondered if it would be possible to replace it with electrical epidural stimulation of the spinal cord with a decerebrated rat model. On an acute preparation of 16 Wistar rats decerebrated at the precollicular level, the tonic muscles activity, muscles evoked potentials and the possibility of inducing locomotion during electrical epidural stimulation of the spinal cord, were studied. Histological control of the level of decerebration was performed in 10 rats. Quadrupedal walking was induced in five animals, bipedal hindlimb walking – in one animal; the parameters of the evoked locomotion do not depend on the substantia nigra degree of damage. The tonic activity and the amplitude of the sensory component of the evoked potential of the hindlimb muscles (mm. tibialis anterior and gastrocnemius medialis) depend on the rostrocaudal level of decerebration – they are higher when the substantia nigra is damaged. Thus, the model under consideration makes it possible to successfully study muscle tonic activity and evoked muscle potentials; however, the use of this model in the study of controlled locomotion requires additional research.