Vol 55, No 5 (2019)

The problems of individual sensitivity and tolerance of an organism to environmental exposures refer to most fundamental challenges of physiology being tackled for a long time. Meanwhile, different authors may be at variance in interpreting the terms “sensitivity” and “tolerance”. This review summarizes literature data on the issues of interpreting and assessing sensitivity and tolerance to hypoxia. A special focus is on those studies which compare the initial individual response of an organism to hypoxia and its viability at subsequent stages of hypoxic and other extreme exposures. When resolving these issues, it is necessary to allow for the existence of two opposite life support strategies, active and passive. The first strategy takes advantage of early detecting detrimental exposures and mobilizing energy resources aimed at their avoidance. The second strategy implies saving (instead of mobilizing) energy resources due to hierarchical functional activity limitation (downregulation) which allows an organism to survive exposure as long as possible at relatively low sensitivity and reactivity. The existence of the second strategy disallows unambiguous interpretation of results of hypoxic tolerance assessment based on analyzing functional disorders, such as mental and physical performance decrement and locomotor incoordination, which arise under hypoxic exposures.

The cardiovascular system of vertebrates, including humans, is well known to respond to hyperoxia by vasoconstriction, bradycardia and decreased contractility of the left heart ventricle. We hypothesized that all of these responses are components of the baroreflex that regulates blood pressure and circulation in hyperoxia. To test this hypothesis, we carried out experiments on awake rats in which the dynamics of arterial blood pressure, organ blood flow (brain, kidney, lower limbs) and ECG was tracked in response to oxygen breathing at 1, 3 and 5 ATA. The afferent and efferent baroreflex pathways were studied using denervation of the carotid baroreceptors and transection of the aortic depressor nerves and vagus nerve. The baroreflex effectiveness was assessed using phenylephrine injections or spontaneous changes in blood pressure. To activate the GABAergic system, nipecotic acid was injected into the lateral ventricle of the brain. Our studies demonstrated the presence of all the baroreflex components in hyperoxia which were triggered by a sharp rise in blood pressure due to systemic vasoconstriction. Hyperoxic vasoconstriction, in turn, arose due to endothelium-derived nitric oxide (NO) which binds to superoxide anions followed by a loss of the vasodilator component of vascular tone. Aortic and carotid sinus baroreceptors with ascending nerve fibers were identified as an afferent component of the hyperoxic baroreflex. Bradycardia and a decrease in cardiac output, resulting from baroreflex activation by hyperoxia, are actualized via efferent sympathetic and parasympathetic pathways. At 1 and 3 ATA the baroreflex effectiveness increased compared to atmospheric air breathing, but extreme hyperoxia (5 ATA) suppressed the baroreflex mechanism. Activation of the GABAergic system in the cerebral cortex by nipecotic acid prevented the loss of the hyperoxic baroreflex. In hyperoxia, the baroreflex mechanism realizes adaptive responses of the cardiovascular system aimed at restraining the delivery of excess oxygen to an organism and mitigates activation of the sympathetic nervous system.

The suprachiasmatic nucleus (SCN) of the hypothalamus and the pineal gland (epiphysis) play an important role not only in the regulation of circadian rhythms but also in the implementation of adaptive responses, including those to various stress factors. Age-related morphofunctional changes in these brain structures, including those associated with increased oxidative stress, exert a significant effect on the organism as a whole. The aim of this work was to explore the dynamics and mechanism of apoptosis in pinealocytes and SCN neurosecretory cells as well as to determine the possibilities of pharmacological correcting this process by an antioxidant alpha-tocopherol and an immunomodulator cycloferon under physiological and immobilization stress conditions in young (2–4-month-old) and aged (30-month-old) Wistar rats. The preparations were administered perorally once a day for 14 days. While the apoptosis level increased with age both in the SCN and the pineal gland, administration of alpha-tocopherol, cycloferon and their combination led to abate this process. It was shown that stress-induced apoptosis in the SCN and the pineal gland proceeds via the p53-dependent pathway, while administration of alpha-tocopherol acetate, cycloferon and their combination decreases the apoptosis level in pinealocytes, suppressing p53 expression both in young and aged animals. In the SCN, no relationship was found between apoptosis and p53 expression levels after administration of the above preparations during stress, suggesting the involvement of different mechanisms.

A new hypothesis based on structural and molecular heterogeneity of thermogenic adipocytes suggests that regulated thermogenesis in mammalian adipose tissues involves two structural-functional levels. The first level comprises typical brown fat and beige adipocytes of subcutaneous white fat depots. Being a part of the functional thermoregulatory system, this level of heat production is controlled by the appropriate hypothalamic centers. The second level is represented by visceral beige adipocytes with a relatively low total thermogenic capacity which provide a fine local adjustment of thermal optima for cell renewal processes. This level is regulated mainly by the local auto- and paracrine mechanisms.

Our study addresses the effect of repetitive sessions of hyperbaric oxygenation (HBO) (2 ATA, 50 minutes, 1 session a day) on superoxide dismutase (SOD) activity as assayed by a chemiluminescent method in the phylogenetically heterogeneous brain structures (brain stem, cerebellum, cerebral hemispheres) of white rats. A study of intact animals (series 1, control) revealed no statistically significant differences in SOD activity between these structures. One HBO session (series 2) stimulated SOD activity in all the brain structures: in the hemispheres, cerebellum and stem by 41, 31 and 66% vs. control, respectively (p < 0.05). After five HBO sessions (series 3), the SOD response intensity in the brain stem exceeded that in the other structures (p < 0.05) and increased by 187% vs. control (p < 0.001). Further continuation of oxygenation up to ten sessions (series 4) was accompanied by a normalization of SOD activity. After eighteen HBO sessions (series 5), the SOD activity level in the cerebellum and cerebral hemispheres somewhat increased compared to the 10th HBO session, although remained closer to the values of the control group than to those of the brain stem. In the brain stem, the SOD activity level exceeded that in intact rats by 46% (p < 0.05).