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P.5.077 Effect of docosahexaenoic dopamine oncerebral circulation in rats after global reversible brain ischemia
Poster Sessions
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significantly decreases cerebrovascular effect ofafobazole. It was shown that, during blockade of GABAA receptors by bicuculline and picrotoxin (0.5mg/kg), afobazole causes increases in cerebral circulation by 11.4-t-2.7% and 10.6+2.7%, respectively (P<0.05). Investigation of picamilon (10mg/kg, intravenously) showed that its cerebrovascular effect did not change during blockade by bicucullin and was significantly reduced during blockade of chloric channels of GABAA receptors by picrotoxin. The picamilon-induced improvement of microcirculation in intact rats was found to be 41.4+10.4%, while it was only 7.9-t-3.5% in the presence of picrotoxin (P <0.01). These findings indicate that picamilon's effect depends on chloric channels of GABAA receptors. It was shown that the cerebrovascular effect of afobazole is significantly attenuated during blockade of GABAA receptors. This provides evidence for an important role of the GABA system in the cerebrovascular and neuroprotective activity of afobazole.
References [1] M.G. Balasanyan, 2003. Afobazole and prevention of anxiety induced focal cerebral ischemia. In: Abstract book of the Second Congress of the Russian Pharmacological Society, Fundamental Problems of Pharmacology vol. 1, p. 57 [in Russian]. [2] S.B. Seredenin, T.A. Voronina, G.G. Neznamov, 1998. Pharmacogenetic conception of anxioselective effect. Vest. RAMS 1 1 : 3 - 9 [in Russian].
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Effect of docosahexaenoic dopamine on cerebral circulation in rats after global reversible brain ischemia
N.A. Khailov, V.V. Bezuglov, N.M. Gretskaia. Laboratory
of Pharmacology of Corebrovascular Disorders, State Zakusov's Institute of Pharmacology Russian Academy of Medical Sciences, Baltiyskaya str 8, 125315 Moscow, Russia The pharmacotherapy of cerebrovascular ischemic disorders is an actual problem at present. A series of original dopaminamides of polyunsaturated fatty acids were investigated and characterized with respect to cerebrovascular stimulant properties at the Institute of Pharmacology RAMS. Experiments were made on anesthetized rats. Local cerebral blood flow in rats was registered by laser doppler flowmeter. Experiments showed that the dopaminamides of arachidonic, eicosapentaenoic, and docosahexaenoic acids stimulated local circulation in the cerebral cortex and increased the brain microcirculation in rats. The most pronounced cerebrovascular effect was
produced by docosahexaenoic dopamine (DI--IEA dopaminamide) (0.2 mg/kg, given intravenously). The effects of DHEA dopaminamide on cerebral circulation were clearly recognized after global reversible brain ischemia and in the model of ischemic state during radial gravitational overloads. The experiments showed that following global reversible brain ischemia DHEA effects on the cerebral circulation were more pronounced than those observed in intact rats (61.85-t- 15.2%, in comparison with 63.8-t-9.60%). In special experiments, radial gravitational overloads in craniocaudal direction, during which the pressure in cerebral arteries dropped to zero, was used as ischemic state model. The DHEA was found to increase survival of rats by 3.0min in this model of ischemic state. As known, dopamine is an expressive cerebral vasoconstrictor. We compared its effects with those of DHEA dopaminamide. Our experiments showed that DHEA dopaminamide influenced the cerebrovascular effect of dopamine. The ability of DHEA dopaminamide to increase cerebral blood flow after ischemia plays an important role in its neuroprotective effects. It was shown that docosahexaenoic dopamine had a direct dilatatory effect on cerebral vessels. At the same time the substance increased also the arterial blood pressure (69+7.2%) as compared with that in intact rats (53.4-t-6.2). The data obtained suggest that DHEA dopaminamide and related substances could be promising for the development of new approaches to regulation of brain microcirculation and arterial blood pressure.
IP.5.0781 Acute focal cerebral ischemia and coenzyme Q O.V. Povarova, E.I. Kalenikova, O.S. Medvedev.
Department of Pharmacology, Lomonosov Moscow State University, 31/5, av. Lomonosoo, Moscow, Russia After ischemic stroke the production of reactive oxygen species may increase, leading to brain tissue damage and subsequent cell death by necrosis or apoptosis. The damage can amplify due to weakened cellular antioxidant defence systems, in particular the component of the second defence line - coenzyme Q (CoQ, ubiquinone) well known as an electron and proton carrier in mitochondrial electron transport. So, treatment with antioxidants may prevent propagation of tissue damage and improve both the survival and neurological outcome. In this connection the purpose of our study was to estimate the influence of acute cerebral ischemia on the brain content of CoQ and to study the effect of ct-phenyl-t-butyl-nitrone - a spin-trap scavenger (PBN) - as antioxidant on these changes. Ipsilateral focal ischemia was induced in 4-monthold male Wistar rats (weight, 350 to 400g). Animals
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significantly decreases cerebrovascular effect ofafobazole. It was shown that, during blockade of GABAA receptors by bicuculline and picrotoxin (0.5mg/kg), afobazole causes increases in cerebral circulation by 11.4-t-2.7% and 10.6+2.7%, respectively (P<0.05). Investigation of picamilon (10mg/kg, intravenously) showed that its cerebrovascular effect did not change during blockade by bicucullin and was significantly reduced during blockade of chloric channels of GABAA receptors by picrotoxin. The picamilon-induced improvement of microcirculation in intact rats was found to be 41.4+10.4%, while it was only 7.9-t-3.5% in the presence of picrotoxin (P <0.01). These findings indicate that picamilon's effect depends on chloric channels of GABAA receptors. It was shown that the cerebrovascular effect of afobazole is significantly attenuated during blockade of GABAA receptors. This provides evidence for an important role of the GABA system in the cerebrovascular and neuroprotective activity of afobazole.
References [1] M.G. Balasanyan, 2003. Afobazole and prevention of anxiety induced focal cerebral ischemia. In: Abstract book of the Second Congress of the Russian Pharmacological Society, Fundamental Problems of Pharmacology vol. 1, p. 57 [in Russian]. [2] S.B. Seredenin, T.A. Voronina, G.G. Neznamov, 1998. Pharmacogenetic conception of anxioselective effect. Vest. RAMS 1 1 : 3 - 9 [in Russian].
•
Effect of docosahexaenoic dopamine on cerebral circulation in rats after global reversible brain ischemia
N.A. Khailov, V.V. Bezuglov, N.M. Gretskaia. Laboratory
of Pharmacology of Corebrovascular Disorders, State Zakusov's Institute of Pharmacology Russian Academy of Medical Sciences, Baltiyskaya str 8, 125315 Moscow, Russia The pharmacotherapy of cerebrovascular ischemic disorders is an actual problem at present. A series of original dopaminamides of polyunsaturated fatty acids were investigated and characterized with respect to cerebrovascular stimulant properties at the Institute of Pharmacology RAMS. Experiments were made on anesthetized rats. Local cerebral blood flow in rats was registered by laser doppler flowmeter. Experiments showed that the dopaminamides of arachidonic, eicosapentaenoic, and docosahexaenoic acids stimulated local circulation in the cerebral cortex and increased the brain microcirculation in rats. The most pronounced cerebrovascular effect was
produced by docosahexaenoic dopamine (DI--IEA dopaminamide) (0.2 mg/kg, given intravenously). The effects of DHEA dopaminamide on cerebral circulation were clearly recognized after global reversible brain ischemia and in the model of ischemic state during radial gravitational overloads. The experiments showed that following global reversible brain ischemia DHEA effects on the cerebral circulation were more pronounced than those observed in intact rats (61.85-t- 15.2%, in comparison with 63.8-t-9.60%). In special experiments, radial gravitational overloads in craniocaudal direction, during which the pressure in cerebral arteries dropped to zero, was used as ischemic state model. The DHEA was found to increase survival of rats by 3.0min in this model of ischemic state. As known, dopamine is an expressive cerebral vasoconstrictor. We compared its effects with those of DHEA dopaminamide. Our experiments showed that DHEA dopaminamide influenced the cerebrovascular effect of dopamine. The ability of DHEA dopaminamide to increase cerebral blood flow after ischemia plays an important role in its neuroprotective effects. It was shown that docosahexaenoic dopamine had a direct dilatatory effect on cerebral vessels. At the same time the substance increased also the arterial blood pressure (69+7.2%) as compared with that in intact rats (53.4-t-6.2). The data obtained suggest that DHEA dopaminamide and related substances could be promising for the development of new approaches to regulation of brain microcirculation and arterial blood pressure.
IP.5.0781 Acute focal cerebral ischemia and coenzyme Q O.V. Povarova, E.I. Kalenikova, O.S. Medvedev.
Department of Pharmacology, Lomonosov Moscow State University, 31/5, av. Lomonosoo, Moscow, Russia After ischemic stroke the production of reactive oxygen species may increase, leading to brain tissue damage and subsequent cell death by necrosis or apoptosis. The damage can amplify due to weakened cellular antioxidant defence systems, in particular the component of the second defence line - coenzyme Q (CoQ, ubiquinone) well known as an electron and proton carrier in mitochondrial electron transport. So, treatment with antioxidants may prevent propagation of tissue damage and improve both the survival and neurological outcome. In this connection the purpose of our study was to estimate the influence of acute cerebral ischemia on the brain content of CoQ and to study the effect of ct-phenyl-t-butyl-nitrone - a spin-trap scavenger (PBN) - as antioxidant on these changes. Ipsilateral focal ischemia was induced in 4-monthold male Wistar rats (weight, 350 to 400g). Animals