[The authors review the pathomechanism of severe COVID-19 leading to systemic uncontrollable inflammation, thrombotic events and other complications. The review includes the extremely complex interactions between the infecting coronavirus and the in loco cellular-tissue contact system, the kinin-kallikrein and the renin-angiotensin systems. Authors critically evaluate some potential therapeutic interventions aiming at the mitigation of the dominant bradykinin-cytokine storm in the background of severe COVID-19 by inhibiting bradykinin formation, facilitating its degradation, or blocking either the B2 receptor or the bradykinin induced cytokine response.]

[For the first time, we demonstrated the fenestration in the endothelium of the distal portion of renal afferent arteriole (AA), which is unusual among high pressure vessels. The fenestrae are co-localized with renin producing granular epithelioid cells; this arrangement makes it likely that the relatively large renin molecules may use this path to enter into the plasma. We also demonstrated that the length and area of this fenestrated segment 1) correlates with the activity of the renin-angiotensin system (RAS), 2) may change by age, in response to some stimuli such as thirst and in some diseases, 3) allows filtration of fluid prior to the glomerular filtration, which can be as high as about 30% of GFR. This morphology and the high filtration volume in AA is one of the most striking observations of renal microcirculation, and question several basic renal physiological issues.]

[Angiotensin II (Ang II) by activating angiotensin type 1 receptors (AT1R) is one of the most potent vasoconstrictors in the regulation of vasomotor tone and thus systemic blood pressure. In this study, we hypothesized that aging alters Ang II - induced vasomotor responses and expression of vascular mRNA and protein angiotensin type 1 receptor (AT1R). Thus, carotid arteries were isolated from newborn, young, middle age, old and senescent rats and their vasomotor responses were measured in a myograph (DMT-600) to repeated administrations of Ang II. Vascular relative AT1R mRNA level was determined by qRT-PCR and the AT1R protein density was measured by Western blot. Contractions of vessels to the first administration of Ang II increased from newborn to young and middle age rats then they decreased to senescent rats. In general, second administration of Ang II elicited reduced contractions, but they also first increased and then they decreased to old age. Similarly, the AT1R mRNA level and the AT1R protein density increased from newborn to young and middle age rats then they decreased to senescent rats. The pattern of these changes correlated with functional vasomotor data. We conclude that aging (newborn to senescence) has substantial effects on Ang II-induced vasomotor responses and AT1R signaling suggesting that it is - and thus regulation of systemic blood pressure is - determined primarily by genetic programs.]

[Dyslipidaemia is one of the known main risk factors of atherosclerosis by causing endothelial dysfunction that initiates and promotes vascular remodelling. Recent data from experimental and clinical studies suggest the existence of lipoprotein- neurohormonal interactions that may adversely affect vascular structure and function. Elevated lipid levels enhance the activation of the renin-angiotensin system, and, on the other hand, activation of the renin-angiotensin system leads to increased LDL cholesterol biosynthesis and oxidized-LDL uptake. These findings may explain the synergistic effect on cardiovascular risk observed in patients with coexisting hypertension and dyslipidaemia. The combined use of cholesterol-lowering drugs and inhibition of the tissue renin-angiotensin system may be more efficient in reducing cardiovascular risk.]

[The role of the renin-angiotensin system in the regulation of blood pressure is outlined. The mechanism of action as well as the role of angiotensin converting enzyme inhibitors (ACEI) in the treatment of various forms (primary, secondary, uncomplicated, complicated) of hypertension is discussed. The individualized , stepped care" approach is detailed, therefore the advantages of the therapeutic combinations of ACEi-s are emphasized. Interactions with other antihypertensive agents and with other drugs are also described, and side effects are also briefly addressed]