卷 109, 编号 8 (2023)

The ability of skeletal muscles to sense mechanical stimuli and respond to them by changing intracellular electrochemical and biochemical processes (mechanotransduction) is of crucial importance for the regulation of physiological processes in muscle fibers. This review describes the main sarcolemmal, sarcomeric, and cytoskeletal mechanosensitive structures and analyzes mechano-dependent signaling pathways and mechanisms involved in the regulation of gene expression as well as muscle protein synthesis and degradation. The final part of the review formulates specific questions in the field of muscle mechanotransduction that need to be addressed in future studies. Understanding of skeletal muscle mechanotransduction is necessary for the development of effective measures aimed at the treatment of muscular dystrophies, sarcopenia, and prevention of disuse-induced muscle atrophy.

Suppression of the proliferation of vascular endothelial cells and the interaction of endothelial with smooth muscle cells in pulmonary hypertension (PH) are impaired. Participation of the 5-HT2a-receptor in the mitogenic effect on endothelial, and 5-HT2b-receptor – on vascular smooth muscle cells was revealed. The main organ that metabolizes serotonin is the lung. In the endothelial cells of the vessels of the lungs under the action of the enzyme monoamine oxidase And serotonin is converted to 5-hydroxyindoleacetic acid (5-HIAA), which is subsequently excreted in the urine. Currently, the role of 5-HT2-receptors is not taken into account in the treatment of children with pulmonary hypertension. We have modified the monocrotaline model of pulmonary hypertension for immature rats. A scheme for the administration of a 5-HT2-receptor blocker for the prevention and treatment of pulmonary hypertension in immature rats was developed and tested. A positive correlation was found between the concentration of 5-HIAA in urine and the degree of pulmonary hypertension, which can become a potential marker of pulmonary hypertension. The data obtained indicate the development of pulmonary hypertension in immature rats after a single injection of monocrotaline in the form of replacement of lung tissue with fibrous tissue, the development of pneumosclerosis and bronchiectasis. Also, in animals in this model, changes in the structure of the heart muscle and vascular wall are formed with the development of fibrous tissue, which may indicate the involvement of 5HT2-receptors in the activation of fibroblasts and, accordingly, in the pathogenesis of pulmonary hypertension.

Arterial hypocapnia (AH), induced by voluntary or forced hyperventilation of the lungs, is accompanied by a decrease in cerebral blood flow (due to an increase in the arteriole tone) and an increase in the affinity of hemoglobin for oxygen. As a result, an insufficient oxygen supply to cortical tissue take place and zones with a critically low oxygen tension (pO₂) are formed in brain tissue. The distribution of pO₂ to cerebral cortex during AH has not been studied enough. The aim of the work was to evaluate the effectiveness of oxygen supply to brain tissue at the level of arterial and venous microvessels at AH. To do this, the following tasks were set: 1) to study the distribution of the pO₂ on the arterial and venous microvessels of the rat cerebral cortex; 2) to analyze tissue pO₂ profiles near the walls of these microvessels. On anesthetized Wistar rats under conditions of forced hyperventilation (P_aCO₂ = 17.1 ± 0.7 mm Hg), the distribution of oxygen tension on the wall of pial and radial arterioles with a lumen diameter of 7–70 μm and on the wall of pial and ascending venules with a lumen diameter of 7–300 µm was studied. In tissue, near the wall of cortical arterioles and venules with a lumen diameter of 10–20 μm, tissue pO₂ profiles were measured. Measurements of pO₂ during spontaneous breathing of the animal with air served as a control. All pO₂ measurements were made using platinum polarographic microelectrodes with a tip diameter of 3–5 μm. Visualization of the electrode tip and microvessels was carried out using a LUMAM-K1 microscope with epiobjectives of the contact type. This work presents for the first-time direct measurements of pO₂ on the walls of arterioles and venules of the rat cerebral cortex and in tissues at different distances from the walls of these microvessels at AH. It has been shown that AH results in significant decrease in the oxygen supply to cerebral cortex, that is manifested by a significant drop of the pO₂’s on venous microvessels and in tissue in the immediate vicinity of the studied microvessels. It has been shown, that the role of arterioles as a direct source of oxygen to brain tissue, is significantly reduced during arterial hypocapnia. Forced hyperventilation results in significant deterioration of oxygen supply to cerebral cortex, despite elevated pO₂ values in the systemic arterial blood and in blood of systemic cerebral veins (sagittal sinus).

Reactions of pial arteries to exogenous hydrogen sulfide exposure and assessment of the contribution of K_ATP and BK_Ca-channels to H₂S-mediated dilation was studied in rats of different ages. Intravital microphotography in Sprague-Dawley rats aged 4 and 18 months was used to study the reactions of pial arteries of various diameters to the exposure of exogenous hydrogen sulfide donor solution – sodium hydrosulfide (NaHS, 30 μM), as well as their change with the preliminary use of potassium channel blockers: K_ATP (glibenclamide, 10 μM) and BK_Ca (tetraethyl ammonium, 2 mM). It was found that inhibition of H₂S-mediated dilation of pial arteries and increase in constrictor responses to exogenous hydrogen sulfide exposure are taking place in rats with age. Age-related changes in H₂S-induced dilatory response of the pial arteries in rats depend on the size of the vessels. With age, there is a decrease in the number of dilations of pial arteries with a diameter of more than 20 μm. At the same time, aging does not affect the dilatation of smaller arteries. These disorders are probably associated with changes in the processes caused by the activation of potassium channels. It was found that aging is accompanied by the increasing of K_ATP-channels contribution to the implementation of H₂S-mediated dilation in pial arteries with diameters less than 40 μm. BK_Ca-channels contribution to the dilatation decreases with age. In 18 months, rats, these channels barely participate in H₂S-mediated dilation in arteries with diameters more than 20 μm.

A comparative analysis of heart rate variability (HRV) indices after injection of the acetylcholinesterase inhibitor (AChE) physostigmine (¾ LD₅₀) and the T-type calcium channel blocker (T-VDCC) Ni²⁺ (ED₁₀₀) into animals was performed in experiments on 3-day-old newborn rats. Both drugs cause phenomenologically similar pathological heart rhythm with significant bradycardia complexes (PHRBC). Analysis of HRV indices showed that the disturbance of heart rhythm regulation mechanisms in NiCl₂ poisoning of rats and in cholinoreactive structure activation caused by AChE inhibition develop according to a similar pattern. In both cases there is a decrease in the total power of the spectrum and the absolute power values of the LF (predominantly sympathetic) and HF (parasympathetic influences) bands. Significant decrease in the level of nerve influences leads to the fact that the dominant role in the regulation of heart rhythm begins to play neurohumoral factors (VLF-band). It was found that under conditions of premedication with H- or M-cholinolytics, when rats do not develop cardiac rhythm disturbances, the initial decrease in the severity of neurohumoral and subsequent increase in sympathetic and, to a lesser extent, parasympathetic influences is common. In this case, vagosympathetic balance is not decisive. In case the influence of neurohumoral factors increases after premedication, then later there is a decrease in the proportion of nerve influences and the occurrence of PHRBC. The obtained data suggest that in newborn rats both direct blockade of T-VDCC and changes in I_CaT current mediated through M₃-subtype muscarinic cholinoreceptors lead to disruption of pacing and development of PHRBC.