Considering the available data that the imbalance in operation of the peptides which are formed as a result of action of ACE1 and ACE2 strengthens action of Angiotenzina-II (ANG II), and it is the major driving factor of a pathogeny of COVID-19, were suggested by a number of authors about a possibility of use of inhibitors of an angiotensin-converting enzyme (ACEI) and blockers of receptors of angiotensin (ARB) for treatment of this pathology.
Researches on assessment of effects of inhibition of signaling of angiotensin 2 (ANG II) by introduction of ACEI or ARB for reduction of damage of lungs in a number of experimental models, including ORDS and pulmonary fibrosis are conducted. For studying of pulmonary fibrosis on rodents bleomycin — peptide which is received from a natural compound is widely used and apply to cancer chemotherapy. Bleomycinum damages a pulmonary epithelium, initiating thus fibrosis; at the same time damage of lungs and fibrosis can be reduced treatment by the drugs ACEI/ARB. Reduction of level of defeats and fibrosis after treatment of ACEI/ARB is observed also in other models of pulmonary fibrosis, for example, at gamma irradiation. It is supposed that ACEI/ARB reduce degree of apoptosis of epithelial and other types of cells. It means that initiation of damage of lungs requires signaling of ANG II for start of the pathological answer.
How can it occur? Increase in local signaling renin-angiotenzinovoy of a system (RAS) in lungs promotes damage of lungs and helps to explain efficiency of ACEI/ARB in treatment of this pathology. The additional proof of this mechanism is decrease in the defeat and fibrosis caused by Bleomycinum at the expense of anti-semantic oligonucleotides against angiotensinogen.
Data from other in Vivo models confirm usefulness of ACEI/ARB for decrease in damage of lungs, especially an epithelium that in addition indicates a role of ANG II in providing these effects. It was shown also in researches in public, for example, decline in mortality from pulmonary insufficiency by means of intake of the captopril appointed to the patients receiving full radiation of an organism before transplantation of haematopoietic stem cells. ACEI reception also reduces the radiation induced pneumonitis at patients with lung cancer.
Data of the retrospective researches conducted with participation of people show that ACEI can also prevent or reduce weight of pneumonia. Besides, treatment of ACEI/ARB at the chronic obstructive pulmonary disease (COPD) reduces inflammation, associated diseases and complications of a disease. The retrospective analysis also allows to assume that treatment of ACEI/ARB can facilitate consequences of a radiation pneumonitis. Nevertheless, data of prospective clinical trials with ACEI/ARB at these types of pulmonary defeat are absent.
Researches in the culture of cells give additional data. ANG II induces apoptosis in epithelial cellular lines of the person and in II pnevmotsita at rats. These effects are blocked by addition of ACEI or ARB. Such data were reproduced with use of a lozartan in the same types of cells.
Thus, today there are data that signaling of ANG II through certain receptors plays the central role in damage of lungs. Suppression of these effects through ACEI or ARB has beneficial influence on control of such defeat, including in the context of the acute pulmonary damage caused by an infection.
Thus, researches are necessary for determination of interrelations between a use/dosage of ACEI/ARB and severity of a disease and also mortality. Certain researches of this sort are available, but more information, especially in connection with presence of uncontrollable factors at such researches, including the associated diseases influencing COVID-19 is required from patients. The international databases in which use of ACEI and ARB before hospitalization with the indication of clinical results at patients with COVID-19 is estimated will be very useful to performance of similar researches and to determination of possible differences between patients in the different countries.
Thus, the hypothesis existing today means that the patients receiving therapy by antagonists of ACEI and ARB according to indications have to continue intake of these drugs. Also it is supposed that these drugs can have treatment-and-prophylactic action at treatment of the patients who caught COVID-19, especially at the most vulnerable patients to this viral infection (for example, people are more senior than 70 years or the person with the accompanying pathology).