Influence of new 2-pyrrolidone derivatives to change vasodilative function of vascular endothelium in experimental cerebral ischemia
Aim. To study the endothelial activity of new 2-pyrrolidone derivatives in experimental cerebral ischemia. Materials and Methods. The work was performed on 60 male rats of Wistar line. The model of permanent right-sided occlusion of the middle cerebral artery was used as an experimental model of cerebral ischemia. The test objects - new derivatives of 2-pyrrolidone encoded PirPR, PirA and PirB, and a reference drug - piracetam, were administered after the reproduction of ischemia and within the next 3 days at a dose of 250 mg/kg. On the 4th day the changes in the vasomotor function of endothelium were evaluated in conditions of modification of the synthesis of endogenous nitric oxide. Results. In the course of study it was found that the use of the studied substances and of the reference drug facilitated increase in the velocity of cerebral circulation as compared to the group of animals not given pharmacological support: PirPR - 39.3% (p<0.05), PirA - 33.9% (p<0.05), PirB - 23.4% (p<0.05), piracetam - 25.4% (p<0.05). Besides, with the introduction of the studied substances and of the reference drug, the restoration of vasodilating function of the vascular endothelium was observed, expressed in preservation of vascular response to acetylcholine and nitro-L-arginine methyl ether, and also in reduction of the ‘L-arginine paradox’ phenomenon (a significantly less increase in the velocity of cerebral blood flow in rats receiving the studied substances and piracetam, in response to the introduction of L-arginine, than in the group of negative control animals). At the same time, the effect of the test compounds was comparable with that of the reference drug - piracetam. Conclusion. Based on the obtained data, it can be assumed that the new derivatives of 2-pyrrolidone PirPR, PirA and PirB possess endotheliotropic activity comparable to the reference drug - piracetam, which makes these compounds promising for further study in order to create a cerebroprotective agent with endotheliotropic effect.