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The renin-angiotensin-aldosterone system (RAS) plays a significant role in the regulation of the water and electrolyte balance. Renin from the kidneys converts angiotensinogen to angiotensin I. Angiotensin converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II. The activation of AT1 receptors by angiotensin II causes vasoconstriction, an increase in aldosterone secretion, and an increase in the reabsorption of sodium ions in nephrons, leading to elevation of the blood pressure. Angiotensin II promotes oxidative stress, growth and proliferation of cells, stimulates coagulation, inhibits fibrinolysis, and intensifies inflammatory processes. The ACE-angiotensin II-AT1R pathway is balanced by angiotensin converting enzyme 2 (ACE2), which degrades angiotensin I to angiotensin (1-9) and angiotensin II to angiotensin (1-7). Angiotensin (1–7) and angiotensin (1–9) pathways exert protective effects by activating, respectively, Mas and AT2 receptors. ACE and ACE2 also have intimate roles with the plasma kallikrein-kinin system (KKS), a hormonal pathway that modulates the intrinsic blood coagulation system, endothelial cell growth and angiogenesis, the complement pathway and RAS. The appearance in Wuhan, China, of the first cases of SARS-CoV-2 infections at the end of 2019 launched a series of intensive studies, which proved that the virus invades host cells using ACE2 as a specific receptor. This survey presents basic information on the structure and tissue distribution of ACE2 and the role this enzyme plays in pathogenesis of COVID-19. A particular emphasis is given to pathophysiological effects of the functional superiority of the ACE → angiotensin II → AT1 receptor axis over the pathway ACE2 → angiotensin II → angiotensin (1-7) → Mas receptor. Such disharmony is a consequence of SARS-CoV-2 induced ACE2–downregulation. In the era of the expanding COVID-19 pandemic, intensive research is conducted not only on vaccines and antiviral drugs, but also on compounds that can restore the functional balance between angiotensin II and angiotensin (1-7).

The aim of our research – to analyze the mechanisms of regulation of the body's proteolytic systems during inflammation, detection of inflammation markers in blood and prostate secretions in the simulation of chronic prostatitis (CP) in rats. 1. The leading link in the pathogenesis of many diseases is a change in the structure and functions of biological membranes – membranopathy, the consequence of which is a violation of histochemical barriers, which is manifested in an increase in the excretion of certain metabolites in the extracellular fluid. In the case of experimental CP in rats, the appearance in the secretion of the prostate gland of the components of KKS, which are determined in the secretion of the normal prostate in trace amounts, was noted. Inflammatory damage to the prostate was also evidenced by an increase in the proteolytic potential of prostate secretion due to an increase in kallikrein activity on the 21st day by 807.1% (р˂0.05), which leads to massive kininogenesis. Depletion of the adaptive and compensatory potential of the prostate gland was evidenced by a decrease in prekallikrein by 21.7% (р˂0.05) compared to the intact group of animals. A sharp increase in the activity of kallikrein in CP is probably compensated by an increase in the activity of its specific inhibitor – α2-macroglobulin, the level of which in the secretion of the CP increased on 225 % on the 21st day of the experiment compared to intact rats, and the increase in proteolytic potential – by an increase of 125 % in the inhibitory activity of α1-PI, a protein of the acute phase of inflammation. An increase in the content and activity of KKS components in the secretion of the prostate testifies to its inflammatory damage and violation of the permeability of the hematoprostatic barrier, which can be an important diagnostic criterion.

Kallikreins cleave kininogens to release kinins. Kinins exert their biological effect by activating constitutive bradykinin receptor-2 (BR2) and inducible by inflammatory cytokines bradykinin receptor-1 (BR1). Studies in animal models and some clinical observations indicate tat the activation of kallikrein - kinin system may have relevance to central nervous system (CNS) diseases, including multiple sclerosis, Alzheimer's disease, epilepsy as well as cerebral ischemia and neoplasmatic tumors. The actions of kinins include vasodilatation and increased vascular permeability may contribute to blood-brain barrier disruption. Kinins evoke pain, and stimulate of endothelial cells, white blood cells, astrocytes and microgia cells to release of prostanoids, cytokines, free radicals, nitric oxide. Kinins stimulate angiogenesis and proliferation of tumor cells. These events lead to neural tissue damage and long lasting disturbances in blood-brain barrier function. In animal models the overexpression of genes and proteins of tissue kallikrens, kininogen as well as RB1 and RB2 has been observed. Kinin receptors antagonists, especially B1R blockade decreased morphological and biochemical features of CNS inflammation. On the other hand in brain tumor models RB1 and RB2 activation has been shown to mediate reversible blood-brain barrier permeability to enhance anti-cancer drug delivery, which may have therapeutic potential.