Use of profetur in acute arterial hypotension caused by ace inhibitors

Abstract

Introduction. ACE inhibitors are well known to improve outcomes in the prevention of acute myocardial infarction, lowering the morbidity and mortality in congestive heart failure, and to attenuate renal dysfunction. On the other hand they can induce severe refractory hypotension during general anesthesia or in case of overdose. Profetur is a new alkylisothiourea derivative with potent antihypotensive vasoconstrictive action. The substance has a long lasting action after single dose administration, both in normal conditions and on the background of blockade action of different antihypertensive drugs. This characterizes profetur as a promising drug for the use in the treatment of acute arterial hypotension caused by ACE inhibitors. Aim of the study. Evaluation of the possibility of using of the new antihypotensive vasoconstrictive isothiourea derivative profetur for the correction of hemodynamic disorders observed in acute arterial hypotension caused by ACE inhibitors. Material and methods. Experiments were performed on rats anaesthetized by sodium thiopental (30-50 mg/kg, i/p). Acute arterial hypotension was modeled by intravenous administration of the ACE inhibitor enalapril (2 mg/kg). In order to correct hemodynamic disorders, profetur was administered intravenously in the dose of 20 mg/kg. Antihypotensive action was assessed by determining changes in blood pressure, heart rate and respiration in the initial state, after 2 and 15 minutes on the background of enalapril, and within 60 minutes after the administration of profetur. Results. Enalapril administration was accompanied by a decrease in blood pressure by 32.5%, an increase in heart rate by 4.6% and respiratory rate by 33.5%. With a single intravenous administration of profetur, blood pressure was significantly increased and stabilized (106±21,1- 114,7±20,6 mmHg) during the whole duration of the experiments. Recovery of blood pressure was accompanied by a decrease in heart rate and respiration. Changes of these parameters indicate that the profetur, normalizing blood pressure, eliminated hemodynamic disorders caused by enalapril. Conclusions. In acute arterial hypotension caused by enalapril, profetur preserves its vasoconstrictive action and contributes to abolishment of the disturbances of the systemic hemodynamics and hypoxia seen with the use of the ACE inhibitor.