The study of the mechanisms underlying the increased vulnerability of the individual to stressful environmental factors in different age periods is of great relevance for prevention and effective treatment of stress-dependent diseases that are widespread in the population of aging individuals. The purpose of our study was to investigate the individual and age-related features of the glucocorticoid negative feedback in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, the key adaptive neuroendocrine system, in experiments with physically healthy young and old female rhesus monkeys with administration of mineracorticoid receptor (fludrocortisone) and glucocorticoid receptor (dexamethasone) agonists. We studied the monkeys with increased trait anxiety and depression-like behavior (DAB) characterized, as previously was shown, by the increased vulnerability to acute stress and the animals with normal standard behavior (SB) as the control. The pronounced individual differences in the reaction of HPA axis to fludrocortisone and dexamethasone in young animals were found. Young animals with DAB showed a lower sensitivity of HPA axis to the inhibitory effect of both fludrocortisone and dexamethasone compared with young animals with SB. At the same time, there were no significant intergroup differences in the concentration of ACTH and cortisol in response to placebo injection, i.e., in basal conditions. The old individuals with DAB demonstrated the essential relative resistance of HPA axis to fludrocortisone test and higher basal plasma levels of cortisol and ACTH in the evening (the period of HPA axis low circadian activity) compared to old SB animals. In the same time, the intergroup differences in the response of HPA axis to dexamethasone administration were leveled due to age-related increase in sensitivity of HPA axis to dexamethasone in animals with DAB. These data testify the pronounced intergroup and age differences in the feedback regulation of HPA axis, presumably resulting from unequal individual, and age-related changes in the activity of mineralcorticoid and glucocorticoid receptors in the brain structures supporting the functions of HPA axis. The maximum age disorders in functioning of the negative feedback mechanism in the regulation of HPA axis are characteristic of animals with DAB, which, apparently, underlie the increased vulnerability of these animals to stress exposure.

Male ISIAH rats with inherited stress-induced arterial hypertension (BP 174.0 ± 1.3 mm Hg) received antagonist of angiotensin II receptors losartan in a dose of 10 mg/kg/day for 16 days. Ultrastructural study of the right atrium showed signs of dramatic and pronounced inhibition of synthesis of the natriuretic peptides (changes in the composition of secretory granules and decrease in their population density and size) the atrial myocytes against the background of persistent BP decrease in hypertensive rats to 142.0 ± 4.2 mm Hg. We concluded that myoendocrine cells in rats with stable hypertension retain ability to respond adequately to distention of the atria with blood.

New research on Methylene Blue (MB), carried out in 2020, shows that it can be an effective antiviral drug as part of COVID-19 treatment. According to the research findings, MB has potential as a direct antiviral drug for the prevention and treatment of COVID-19 in the first stages of the disease. However, the MB accumulation by various types of tissues, as well as by immune cells, has not been previously studied. Therefore, the objective of this study was to obtain spectral data on the interstitial distribution of the administered drug in endothelial tissues in primates. The data on interstitial MB distribution obtained by spectroscopic measurement at both macro- and microlevels during oral administration to Hamadryas baboon individuals demonstrate that MB accumulates in mucous membranes of gastrointestinal tract and the tissues of the respiratory, cardiovascular, immune, and nervous systems. Additionally, it was found that MB was present in lung and brain myeloid cells in significant concentrations, which makes it potentially useful for protection from autoimmune response (cytokine storm) and as a tool for the correction of immunocompetent cells’ functional state during laser irradiation. Since the cytokine storm starts from monocytic cells during SARS-CoV-2 cellular damage and since tumor-associated macrophages can significantly alter tumor metabolism, accumulation of MB in these cells provides a reason to conclude that the immune response correction in COVID-19 patients and change in macrophages phenotype can be achieved by deactivation of inflammatory macrophages in tissues with MB using laser radiation of red spectral range.

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