Influence exerted by new pyrimidine derivatives on cerebral circulation auto-regulation and vasodilatating function of vessels endothelium in rats' brains under chronic hemic hypoxia
A.V. Voronkov, A.S. Lysenko, A.F. Bandura
Рyatigorsk Medical Pharmaceutical Institute of Volgograd Medical State University, 11 KalininaAvenue, Pyatigorsk, 357532, Russian Federation
Our research goal was to examine influences exerted by new pyrimidine derivatives coded as BL0 and BL2 on cerebral hemodynamics auto-regulation parameters and vasodilatating function of vessels endothelium as risk factors causing ischemic and hemorrhagic strokes under chronic hemic hypoxia.
We performed an experiment on white Wistar rats to prove that endothelial dysfunction which evolves under chronic hemic hypoxia leads to disorders in endothelium-mediated mechanisms for cerebral circulation auto-regulation in rats. We modeled hypoxia in animals via granting them free access to 0.2 % sodium nitrite solution instead of ordinary drinking water. Endothelial dysfunction was confirmed as per disorders in vasodilatation and vasoconstriction reactions at intravenous introduction of acetyl choline (0.1 mg/kg) and methyl ether hydrochloride nitro-L-arginine (10 mg/kg). Cerebral blood flow speed was measured with MM-D-K-Minimax v.2.1. ultrasound Doppler. We assessed cerebral circulation auto-regulation as per compression test results which allowed us to calculate overshoot coefficient and auto-regulation power. Examined pyrimidine derivatives and comparison preparations were introduced orally 60 minutes prior to taking readings. Mexidol doses were calculated on the basis of interspecific recalculation of a maximum daily dose for a man. Nicergoline dose was taken as a most effective one as per literature data.
When new pyrimidine derivatives BL0 and BL2 are applied under chronic hemic hypoxia, it causes overshoot coefficient to grow authentically higher than in a negative control group but it doesn't exert any positive influence on collateral reserve parameter, namely auto-regulation power. BL0 and BL2 improve endothelium vasodilatating function at intravenous acetylcholine introduction (0.1 mg/kg) and don't exert any influence on vasoconstricting function at L-NAME intravenous introduction (10 mg/kg). The examined substance BL0 has more apparent pharmacological effects thus exceeding the second substance BL2 and such comparison preparations as Mexidol and Nicergoline in some parameters.
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