Mechanism of nitric oxide production during brain ischemia studied by near-infrared spectroscopy
Project/Area Number |
10670055
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General physiology
|
Research Institution | National Cardiovascular Center Research Institute |
Principal Investigator |
KANASHIRO Masaru National Cardiovascular Center Research Institute, Laboratory for Comprehensive Experimental Studies, Laboratory Chief, 共通実験室, 室長 (10132929)
|
Project Period (FY) |
1998 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
Keywords | in vivo near infrared spectroscopy / nitric oxide / nitric oxide synthase / NMMA / L-NAME / amino guanidine / 7-nitro indazole / エチルイソチオ尿素 |
Research Abstract |
We have developed a continuous wave near infrared (NIP) spectroscopy system cooperated With an NMR spectrometer. This system includes an apparatus for optical fiber switching, Which apparatous enabled us to obeserve NIP spectra from many regions simultanelusly, and a software package for multicomponent analysis. This system enabled us to ouantitate nitrosyl-hemoglobin (HbNO), as well as oxyhemoglobin, and deoxyhemoglobin, and evaluate the nitric oxide synthase (MOS) activity. Applying this system to an adult and a juvenile gerbil head in 5% oxygen revealed that the hypoxia was severe for an adult gerbil to produce nitric oxide (NO) detected as HbNO whereas it was mild for a juvenile and no NO Was produced. In another experiment on an adult gerbil, occlusion of each carotid artery was also mild to produce no NO.When reperfused, however, NO production on the occluded side was turned on while that on the other side remained off. To clarify whihch MOS('s) is (are) responsible for these rapid, vast production of NO, we carried out a series of inhibitor experiments. Non-selective inhibitors of NMMA and L-NAME inhibited the hypoxic HbNO production, which means the NO relevant to the HbNO production is produced by MOS.An iNOS production. On the other hand, an nNOS inhibitor, 7-nitroindazole (7-NI), showed mild inhibition. All these results suggests the hypoxic HbNO production is due to the two constitutive enzymes of nNOS and eNOS.The vast NO production by cNOS Would be possible if enough amount of Ca2+ is present in cytosol through the Ca release from sarcoplasmic reticulum or the influx of external Ca due to cell dysfunction. selective inhibitor of aminoguanidine (AG) did not show any inhibition of the hypoxic HbNO
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Report
(4 results)
Research Products
(17 results)