Basic Requirements And Features Of Methodology Of The Vascular Permeability Model

D.S. Gajdaj(1), E.A. Gajdaj(1), K.L. Kryshen(2), М.N. Makarova(3), V.G. Makarov(3) 1-Institute of pre-clinical studies Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, Zavodskaya st., b. 3, 245, 188663, Russia; 2-St.Petersbug institute of pharmacy Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, Zavodskaya st., b. 3, 245, 188663, Russia; 3-Scientific-Production Organization «Houm оf Pharmacy» Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, Zavodskaya st., b. 3, 245, 188663, Russia; Е-mail: gajdaj.ea@doclinika.ru

Abstract

This model is used to evaluate the inhibitory activity of drugs aimed at vascular permeability normalization. The barrier function of endothelium is disrupted on some pathologies. The factors affecting an acute increase vascular permeability include natural agents such as thrombin, histamine, bradykinin, reactive oxygen and nitrogen, vascular endothelial growth factor (VEGF), tumor necrosis factor, bacterial endotoxins, necrotic toxins and excessive mechanical stimulation. As a consequence, fluid and plasma proteins are extravasated and edemas are formed. These effects are counteracted by H1-antihistaminics, inhibitors of arachidonic acid metabolism, by leukotriene receptor antagonists and membrane stabilizing drugs are able to reduce capillary permeability. In experiment vascular permeability is increased by intracutaneous injection of the mast cell-degranulating compound 48/80. The vascular permeability can be assessed by Evans blue dye. The main requirements and peculiarities of methodology of vessels permeability model are considered in the article. Within this model, increase in vascular permeability is caused by intradermal injection of compound 48/80, and is confirmed by infiltration of Evans blue dye into the injected skin areas. The vessels permeability is assessed by measuring diameter of colored skin areas and extracting of Evans blue dye. The experimental model shows that intradermal administration of compound 48/80 leads to increase in the permeability of rat skin vessels. The standard object phenylephrine with intraperitoneal administration to rats at a dose 15 mg/kg statistically significant reduces vascular permeability. The dose of Evans blue dye optimal for this type of the study and the time interval at which noted the maximum concentration of dye in tissue, were determined. Based on the results of the studies, it can be concluded that this model is simple, uncomplicated and quite informative.

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