1998 Fiscal Year Final Research Report Summary
Nitroxidergic cerebrocortical vasomotor mechanisms.
| Project/Area Number |
08670073
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
NAKAI Masatsugu Natl.Cardiovasc.Ctr.Res.Inst. Chief Investigator, 循環動態機能部, 室長 (90150226)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Nitric oxide / Cerebral cortex / Cerebral blood flow / Muscarinic receptor / NMDA receptor / Excitatory aminoacid receptors / Periaqueductal gray / Nucleus basalis magnocellularis |
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| Research Abstract |
The periaqueductal gray matter (PAG) is implicated in the central processing of defensive reactions. We found that when stimulated by microinjection of NMDA, the caudal third of the lateral PAG was also capable of increasing cerebral cortical blood flow (CoBF) over widespread cortical areas, which was accompanied by a cortical activation as indicated by observations of enhanced cortical energy metabolism. A substantial proportion of the flow increase was inhibited by the topical cortical application of an inhibitor of nitric oxide (NO) synthase. We found further that the PAG-elicited CoBF increase was sensitive to scopolamine and to MK-801, and attenuated by a chemical impairment of the nucleus basalis magnocellularis (NBM), the latter of which procedure also resulted in a considerable attenuation of cortical ChAT activity. An Ach-induced CoBF increase was highly sensitive not only to scopolamine but also to MK-801. In contrast, a NMDA-induced CoBF increase was sensitive to MK-801, but
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resistant to scopolamine, Synergism between the corticovasomotor actions of Ach and NMDA was very weak.
Overall, we consider that the PAG subdivision provides excitatory inputs to the NBM, which in turn sends off axons to the cortical EAAergic neurons which possess muscarinic receptors. This cholinergic/EAAergic neuron chain may form a major serial link in the central circuitry which emanates from the PAG subdivision and finds its final target site in the cortical primary vasomotor mechanisms. The vasomotor mechanisms may possess NMDA receptors and include the cortical nitroxidergic and metabolic mechanisms.
We further attempted to measure NO contents in the cerebral arterial blood and in the superior sagittal sinus blood so as to estimate cortical production of NO.We found that despite the PAG was stimulatied strongly and thereby resulting in a great increase in CoBF, any detectable difference in NO contents was not observed between arterial blood and sinus blood. We conclude therefore that this approach is of no use for an evaluation of changes in cortical NO production upon physiological stimuli. Less
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