We studied the effect of the purinergic signaling system and the contribution of Cl– transporters to isosmotic contraction of vascular smooth muscle cells (SMC), which results from the normalization of osmotic pressure after prolonged incubation in a hyposmotic medium. The study was carried out by myography of endothelium-denuded aortic ring segments of male Wistar rats. Isosmotic contraction was induced by placing vascular segments in normosmotic Krebs solution (120 mM NaCl) after a 40-minute incubation in a hyposmotic Krebs solution (40 mM NaCl). Purinergic receptors were activated by adenosine 5’-triphosphate (ATP, 500 µM), a nonselective P2X and P2Y receptor agonist, and uridine 5’-triphosphate (UTP, 500 µM), a selective P2Y receptor agonist. ATP and UTP abolished the transience of the aortic SMC isosmotic contraction without affecting its amplitude. Pretreatment of vascular segments with ATP and UTP during incubation in a hyposmotic solution completely suppressed the development of isosmotic contraction in the presence of ATP or UTP, but did not affect it without purinergic receptor activators. The Na+–K+–2Cl–-cotransporter (NKCC) inhibitor bumetanide (100 µM) abolished isosmotic contraction in the presence of ATP (not UTP) but restored its transience. The nonselective Cl– channel and Cl–/HCO3 – exchanger blocker DIDS (100 µM) suppressed the development of isosmotic contraction in the presence of both ATP and UTP. The potassium channel blocker tetraethylammonium (10 mM) potentiated the contractile activity of UTP toward isosmotic volume contraction. Presumably, purinergic receptors abolish the transience of isosmotic contraction by activating Cl– currents through activation of P2Y receptors. The mechanism of interaction between the purinergic signaling system and Cl– transport during cell volume changes requires further investigation.

We studied the effect of the purinergic signaling system and Cl-transporters on vascular smooth muscle cells (SMC) isosmotic striction that occurs when osmotic pressure is normalized after prolonged incubation in a hypoosmotic medium. The study was performed with the method of myography on endothelium-denuded ring segments of the male Wistar rats aorta. Isosmotic striction was induced by placing the vascular segments in normosmotic Krebs solution containing 120 mM NaCl after a 40-minute incubation in a hyposmotic Krebs solution containing 40 mM NaCl. Purinergic receptors were activated by adenosine 5'-triphosphate (ATP, 500 μM) as nonselective P2X and P2Y receptor agonist, and uridine 5'-triphosphate (UTP, 500 μM) as selective P2Y receptor agonist. ATP and UTP eliminated the transient nature of the aorta SMC isosmotic striction without affecting its amplitude. Pretreatment of vascular segments with ATP and UTP during incubation in a hyposmotic solution completely suppressed the development of isosmotic striction in the presence of ATP or UTP, but did not affect isosmotic striction without activators of purinergic receptors. The inhibitor of Na+, K+, 2Cl--cotransport (NKCC) bumetanide (100 μM) abolished isosmotic striction in the presence of ATP, but not UTP, but restored its transient character. A non-selective blocker of Cl– channels and Cl–, HCO3– exchanger DIDS (100 μM) suppressed the development of isosmotic striction both in the presence of ATP and UTP. The potassium channel blocker tetraethylammonium (10 mM) potentiates the constrictor action of UTP on isosmotic striction. We suppose purinergic receptors eliminate the transient isosmotic striction by activating Cl– currents through activation of P2Y receptors. The mechanism of interaction between the purinergic signaling system and Cl– transport during changes in cell volume requires further study.

UNSCEAR has recently increasingly drawn the attention of scientists to studying the consequences of long-term combined (external and internal) exposure to ionizing radiation on the development of ophthalmopathology in the population living in the observation area of an ionizing radiation facility (IRS), and there is little information on this in the available world literature direction. In this regard, it is advisable to study the characteristics of the incidence (the number of newly diagnosed cases of the disease) of diseases of the organ of vision among the personnel of the Siberian Chemical Combine (SCC). For the analysis, information was taken on newly identified cases of diseases of the eye and adnexa (coding according to ICD-10) of all SHC personnel in the period 2012–2022. In the incidence of pathology of the organ of vision, three key places are occupied by pathology of the lens, glaucoma, diseases of the eye muscles with disturbances of concomitant eye movement, disturbances of accommodation and refraction, and diseases of the conjunctiva. The data obtained will be used to improve and adapt the system of medical and biological support for health preservation and extension of working life of the personnel of the Siberian Chemical Combine and other industrial institutes located in the Tomsk region. Keywords: ionizing radiation, long-term technogenic external exposure, ocular surface, morbidity

An electrophysical model of the otolith organs of the vestibular apparatus of a laboratory animal (rat) has been developed using an equivalent electrical circuit. The electrophysical model is presented as a set of conducting and dielectric regions based on the anatomical structure determined from MRI/CT images. The equivalent electrical circuit for the replacement of the otolith organs of the vestibular apparatus of the laboratory animal is based on the measured specific electrical characteristics of the tissues of the otolith structures taking into account the changing ionic conductivity of the hair cells. To determine the spectral sensitivity of otolith organs, the electrical impedance of the cellular elements of the utricle and saccule and the phase shift of the flowing current with respect to an external electrical stimulus were calculated based on the geometric data and electrophysical parameters of the otolith organs of the laboratory animal (rat) in the frequency range 0-5000 Hz. It has been shown that the response of hair cells of the otolith membranes to an external electrical stimulus is oscillatory.

Bilateral asymmetry in the function of the semicircular canals underlies dizziness and vestibular balance disorders. According to the traditional view, otolith dysfunction does not have a significant effect on the clinical picture in individuals with peripheral vestibular disorders. In recent years, interest in studying the contribution of vestibular function to the control of posture and movements has increased. However, we have not identified any studies addressing the reactivity of otolith organs in vestibular balance disorders in the available literature.Aim: To study bilateral otolith reactions in patients with vestibular balance disorders using the method of cervical vestibular evoked myogenic potentials (cVEMP) in patients with episodic and chronic vestibular disorders.Material and Methods. A clinical examination was carried out in 63 patients complaining of dizziness and balance problems. They were hospitalized on an emergency and planned basis in the neurological departments of the clinics of the Siberian State Medical University and the Medical and Sanitary Unit No 2 in Tomsk. From the total group, 28 patients (8 men and 20 women aged from 22 to 84 years) were selected for assessment of vestibular function; the average age was 63.87 ± 11.52 years and 57.2 ± 18.5 years for men and women respectively. They had chronic and episodic vestibular dysfunction unrelated to acute or progressive neurological disease and inflammatory pathology of the inner ear.Results. 27 patients (96.4%) complained of dizziness. Systemic dizziness, characterized by a feeling of objects rotating around the subject, was detected in 29.63% of patients; non-systemic dizziness, including a feeling of “failing” – in 81.48%. Both types of complaints appeared in 10.71% of those examined, which made it possible to identify 2 groups of patients: Group A – with chronic vestibular disorders (7 patients) and Group B – with episodic vestibular disorders (21 patients). During the study of the groups of patients, differences were found in the amplitudes of cVEMP latency P13 and the coefficient of vestibular asymmetry between Groups A and B, as well as the absence of a difference in amplitudes in Group A and the presence of a difference in Group B on the right.Conclusion. Despite the fact that patients presented with predominantly one complaint of dizziness, clinical and instrumental tests of vestibular dysfunction showed the presence of damage to both the semicircular canals and otolithic organs; asymmetry of vestibular reflexes and/or bilateral damage to the vestibular organs. The results of the study allow us to consider the cVEMP method as one of the methods for objectively assessing the condition of the otolithic apparatus in patients with impaired vestibular function. In this regard, it is recommended to use this method in routine neurological practice.

Objective . The role of Cl – -transport in ATP-dependent regulation of contractile activity of rat pulmonary artery (PA) smooth muscle cells was studied. Design and methods . The study was performed on endotheliumdenuded ring segments of the PA of male Wistar rats. Mechanical tension was measured using organ bath technique. Contractions of the PA segments were induced by high-potassium solution (30 mM KCl), hyposmotic solution (40 mM NaCl), as well as restoration of the medium osmolarity (120 mM NaCl) after incubation in hyposmotic solution. Inhibitor of Na + , K + , 2Cl – cotransport (NKCC) bumetanide (10 μM, 30 minutes preincubation), nonselective Cl – -channel blocker SITS (100 μM) and Ca2 + -activated Cl – channels blocker niflumic acid (NA, 10 μM) were used to modulate the Cl – -transport. Results . ATP (10–500 μM) did not affect vascular tone of PA segments incubated in Krebs solution (120 mM NaCl), while 500 and 1000 μM ATP led to the development of transient contractions, the amplitude of which decreased in the presence of bumetanide, SITS and NA. Incubation of PA segments in a hyposmotic medium (40 mM NaCl) caused the development of transient contraction. Subsequent recovery of the medium osmolarity (120 mM NaCl) induced another transient contraction — isosmotic striction. ATP (500 μM) eliminated the relaxation phase of hyposmotic striction, and completely suppressed the development of isosmotic striction. Bumetanide did not affect the action of ATP during isosmotic striction, but restored the relaxation phase of hyposmotic striction. SITS and NA eliminated the effect of ATP on hypo- and isosmotic striction. Conclusions . The constrictive effect of ATP on the smooth muscle cells of the PA is associated with the activation of mechanisms of transmembrane Cl – -redistribution, in which NKCC and Ca2 + -activated Cl – channels are involved.

Purpose. We studied the role of Na+, K+, 2Cl- cotransport (NKCC) in contractile activity of pulmonary artery seg- ments with intact endothelium induced by incubation in nonisosmotic solutions. Materials and methods. The influence of nonisosmotic solutions and blocker of NKCC on vascular segments mechanical tension was studied in isometric regime with organ bath technique performed with the 4-channel Myobath II and software complex LAB-TRAX-4/16 (Germany). Hyperosmotic shrinkage was induced by adding 50-300 mM su- crose to the Krebs solution, the hypoosmotic environment was created by reducing the concentration of NaCl from 70 mM to 40 mM. Bumetanide was used as an NKCC blocker. The amplitude of the contractile responses was evaluated as a percentage of the control contraction in highpotassium solution. Results. The addition of 50-300 mM sucrose to the Krebs incubation solution caused a development of dose- dependent of sustained contractile responses. The amplitude of hyperosmotic striction increased with inhibition of NKCC. Incubation of segments in hypoosmotic solution caused the development of transient contractile responses, the amplitude of which decreased in the presence of NKCC inhibitor. Conclusion. Iincubation of pulmonary artery vascular segments in hyper- and hyposmotic solutions induces con- tractile responses, the amplitude of which depends on the NKCC activity.

Aim. To study the features of regulating the electrical activity and mechanical tension of smooth muscle cells (SMCs) of the guinea pig ureter as modulated by cyclic adenosine monophosphate (cAMP) in hypoxia. Materials and methods. The effects of isoprenaline (100 μM), forskolin (1 μM), 3-isobutyl-1-methylxanthine (IBMX, 100 μM) and tetraethylammonium chloride (TEA, 5 μM) on the contractile and electrical properties of isolated smooth muscle segments of the guinea pig ureter in normoxia and hypoxia were measured by the double sucrose bridge. Hypoxic conditions were created by placing the SMCs in Krebs solution containing (10.0 ± 0.2) vol. % O2. Results. It was found that an increase in the intracellular cAMP level caused by isoprenaline, the β-adrenergic receptor agonist, and activation of adenylate cyclase by forskolin, an inhibitor of phosphodiesterase IBMX, caused a decrease in the electrical and constrictor properties of the SMCs in the guinea pig ureter. The decrease in the level of oxygen in the perfusion solution resulted in the increase in the action potential amplitude and contraction of smooth muscles from the ureter. With an increase in the intracellular cAMP level, the activating effect of hypoxia on smooth muscle segments decreased. Inhibition of potassium conductivity of the ureteral SMCs with TEA in normoxia suppressed the cAMP-dependent processes induced by forskolin, whereas in hypoxia it caused the potentiation of an activating effect on the electrical activity and contractions of smooth muscle segments. Conclusion. Thus, the results suggest the involvement of cAMP-dependent signaling system in the influence of hypoxia on the electrical and contractile properties of ureteral SMCs. Modification of the intracellular cAMP level reduced the stimulatory effect of hypoxia on the smooth muscle strips of the ureter caused by increase in the ionic conductivity of the membrane and contributed to their adaptation to environmental conditions.

The Ca2+-activated potassium permeability of the erythrocyte membrane of healthy donors and patients with arterial hypertension in combination with coronary heart disease was performed with potentiometric method. It is found that the amplitude, rate of development and regeneration of membrane potential (MP) A23187-stimulated hyperpolarizing response (HR) was higher in the erythrocytes of patients as compared to healthy donors. Parameters of redox-stimulated HR, except for the rate of MP recovery, did not differ in both groups of subjects. Modifiers of SH-groups reduced the amplitude of A23187-, but not of redox-stimulated HR in the erythrocytes of healthy donors, and led to a decrease in both A23187-and redox-sti827 mulated HR in the erythrocytes patients. Such changes in Ca2+-dependent potassium permeability of the erythrocyte membrane are associated with impaired structural and functional properties of erythrocytes in the development of cardiovascular pathology.

Objective. To study the effect of the synthetic analog of the platelet activation factor (based on the 1-alkyl-2-alkylcarbamoyl-glycerol) on the tone of vascular smooth muscle cells and hemodynamic parameters. Design and methods. We studied the vasodilator properties of 1-O-hexadecyl-2-O-methylcarbamoylglycerol, the substance from the group of 1-alkyl-2-alkylcarbamoylglycerols. Systemic arterial pressure, stroke volume and heart rate were recorded by the Biopac hardware complex in Wistar rats 3 hours after intragastric administration of the drug. We studied (the Myobath II Tissue bath system) mechanical tension of isolated aortic segments from Wistar and SHR rats precontracted with phenylephrine and nonisosomotic solutions. Using the Wire Myograph 620M system, we recorded changes in the contractility of the small mesenteric arteries, the artery of the gastrocnemius muscle and the renal interlobar arteries of the Wistar rats precontracted with methoxamine. Results. 1-O-hexadecyl-2-O-methylcarbamoylglycerol decreased arterial pressure in Wistar rats after intragastric administration due to the decrease in specific peripheral resistance, but does not exert an evident relaxation acting on isolated vessels pre-reduced by activation of α1-adrenoreceptors with phenylephrin and methoxamine. 1-O-hexadecyl-2-O-methylcarbamoylglycerol reduced the hyper-, hypo-, and isoosmotic contraction of the aortic segments from Wistar rats, but increased (isoosmotic contraction) or did not change (hyper- and hypoosmotic contraction) it in the vessels obtained from SHR rats. Conclusions. The pressure reducing effect of 1-O-hexadecyl-2-O-methylcarbamoylglycerol is not due to direct action on vascular cells. It might involve nervous/humoral mechanisms of blood pressure regulation. However, 1-O-hexadecyl-2-O-methylcarbamoylglycerol reduces the contraction amplitude induced by incubation in the non-isoosmotic environment in normotensive rats. However, the effect is not present in hypertensive rats indicating the possible involvement of NKCC in the mechanisms of the drug substance.

Objective . Hydrogen sulfide (H2S) is one of gasotransmitters that participate in the regulation of a large number of cellular functions. H2S can also act as a pathological link in the development of vascular diseases, in particular hypertension. Na+, K+, 2Cl–-cotransporter (NKCC) might play an important role in vascular tone increasing due to involvement of chloride currents in the depolarization of smooth muscle cell membrane. Significant differences in the regulatory mechanisms of contractile properties of the vessels of systemic and pulmonary circulation might depend on the mechanisms of NKCC. So its role as a target for H2S requires investigation. Design and methods . The changes in mechanical tension of ring segments from pulmonary artery (PA) of WKY and SHR rats under the action of the donor of H2S (L-cysteine) was studied by organ bath technique. Results . L-cysteine caused multidirectional effects on mechanical tension of PA smooth muscle cells from WKY rats precontracted with 30 mM KCl. Bumetanide (100 μM) suppressed the relaxation but not constriction of the intact and endotheliumdenuded vascular segments caused by L-cysteine. In ring segments from PA of SHR rats, L-cysteine potentiated constriction in segments with intact endothelium but caused relaxation in endothelium-denuded segments.

Сероводород является важной сигнальной молекулой, участвующей в регуляции сосудистого тонуса. Методом механографии исследовали роль АТФ-чувствительных, кальций-активируемых и потенциал-зависимых калиевых каналов в механизмах релаксирующего действия сероводорода на сосудистые гладкие мышцы, предсокращенные фенилэфрином – активатором α1-адренорецепторов. Исследование проводили на деэндотелизированных кольцевых сегментах аорты крыс-самцов линии Wistar. В качестве донора сероводорода использовали NaHS. NaHS оказывал расслабляющее действие, близкое к EC50, при концентрации 100 мкМ. Блокатор кальций-активируемых и потенциал-зависимых калиевых каналов тетраэтиламмоний (10 мМ) и избирательный блокатор потенциал-зависимых калиевых каналов 4-аминопиридин (1 мМ) снижали величину расслабления на действие 100 мкМ NaHS, тогда как блокатор АТФ-чувствительных глибенкламид (10 мкМ) калиевых каналов полностью устранял расслабляющее действие 100 мкМ NaHS. Блокатор кальций-активируемых калиевых каналов большой проводимости харибдотоксин (0.1 мкМ) не влиял на величину расслабляющего действия 100 мкМ NaHS. Таким образом, действие сероводорода на гладкие мышцы аорты крысы, предсокращенные фенилэфрином, обусловлено преимущественной активацией АТФ-чувствительных, а также потенциал-зависимых калиевых каналов.

Проявления гипоксии ткани, а также последующей реоксигенации сопровождаются целым комплексом метаболических нарушений, которые приводят, в том числе, к повреждению гладко-мышечных клеток сосудов и нарушению их сократительной функции. Гладкомышечные клетки играют важную роль в регуляции просвета кровеносных сосудов, а следовательно, системного артериального давления и локального снабжения тканей кислородом. Предполагается, что при гипоксии и реоксигенации сосудистых гладких мышц происходит их расслабление и снижение силы сокращений. Механографическим методом было изучено влияние гипоксии и реоксигенации на сократительную активность изолированных гладких мышц аорты крысы на фоне действия α1-адреномиметика фенилэфрина. Проведенные нами исследования показали, что при активации α1-адренергических рецепторов в условиях гипоксии и реоксигенации наблюдается снижение сократительной активности гладкомышечных клеток аорты крысы, причем в большей степени при реоксигенации. Блокирование калиевых каналов плазмалеммы тетраэтиламмонием позволило установить, что угнетающие эффекты гипоксии и реоксигенации на сократительную активность гладкомышечных клеток обусловлены повышением калиевой проводимости мембраны клеток.

The effect of carbon monoxide (CO) on contractile reactions of smooth muscle cells (SMC) caused by depolarization (30mM KCl) and phenylephrine (PE) has been investigated by the mechanographical method. It is shown that the donor CO CORM-2, in experiments with of high potassium contraction in concentrations of 10-1000 µМ, and in cases phenilefrine-induced contractions (10 µМ) of SMC, of 1 µМ and above, caused a dose-dependent relaxation of vascular segments. Inhibition of NO-synthase and soluble guanylate cyclase (GC) weakened CO induced relaxation of the segments. With blocking potassium channels tetraethylammonium chloride and 4-aminopyridine relaxing effect СORM-2 on vascular segments virtually eliminated. These results may be the evidence of cooperation in the implementation of gazotransmitters gasotransmitters relaxating effect of CO on the level of soluble guanylate cyclase and potassium channels plasmalemma of SMC.