The Effect Of Ovp-1 On Blood Pressure And Parameters Of General Hemodynamics In Acute Arterial Hypertension In Rabbits

Abstract

According to the WHO, arterial hypertension (AH) is a world leader among the most common cardiovascular diseases. Despite the achievements of modern medicine, there are many genetic and other factors which determine the further increase in the prevalence of this pathology in our time, including hypodynamics, large-scale use of smartphones and other computer devices, chronic stress, malnutrition, etc. In addition, the difficulty of solving the problem of the prevalence of essential hypertension and secondary symptomatic increase in blood pressure (BP) is associated with the development of a significant number of concomitant cellular and subcellular pathological changes in most organs and systems which can lead to disability and mortality. Modern pharmacotherapy of AH is associated with a significant number of adverse reactions due to the use of antihypertensive drugs, failure of patients to complex and long-term combination regimens, the presence of AH resistant forms. Given the lack of efficacy and unsatisfactory tolerability of antihypertensive drugs, resulting in low motivation of patients to treat, the study of new compounds capable of antihypertensive effects is an important area of modern pharmacological science and practical pharmacy. At the V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine for the last 8 years it has been conducting the synthesis and study in vitro of the vasodilatory properties of oxazole derivatives. Among them, one of the most promising groups of original compounds, which are able to reduce vascular tone, are phosphorylated oxazole derivatives, considering as a new class of potential antihypertensive drugs. In the previous stages, the vasodilating activity presence of the group compound-leader OVP-1 in vitro, antihypertensive action in vivo was experimentally investigated and the safety of this compound was proved. However, the mechanisms of the antihypertensive effect development of OVP-1 stays unclear. Analysis of foreign literature data shows that only one group of original compounds is known, which contain a hydrogenated oxazole ring in their structure and exhibit antihypertensive activity − C07D263 / 34 (USA), the vasodilating effect of which has been confirmed experimentally in vivo and in vitro, based on angiotensin II type 1 receptors blockage and neprilysin inhibition. Neprilysin is a neutral endopeptidase localized in the tissues of the heart and peripheral vessels, capable of inactivating natriuretic peptides, which are responsible for vasodilation. Taking into account the above literature data and our previous experimental studies of phosphorylated oxazole derivatives, it was exprdient to continue the pharmacological study of the vasodilating effect of the leader compound OVP-1 in vivo. The aim of work to evaluate the features of OVP-1 influence on the indicators of systemic hemodynamics under the conditions of experimental modeling of acute arterial hypertension in anesthetized rabbits.