2007 Fiscal Year Final Research Report Summary
Non-invasive Redox Imaging for the Pathophysiological Analysis of Hypertensive Renal Disease and Development of Antioxidative Therapy
| Project/Area Number |
18590878
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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 |
Kidney internal medicine
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| Research Institution | Tsukuba University of Technology (2007)
University of Tsukuba (2006) |
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Principal Investigator |
HIRAYAMA Aki Tsukuba University of Technology, Faculty of Health Sceinces, Professor (20323298)
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| Co-Investigator(Kenkyū-buntansha) |
YOH Keigyou University of Tsukuba, Graduate School for Comprehensive Human Sciences, Associate Professor (90323302)
NAGASE Sohji International University of Health and Welfare, School of Health Sciences, Professor (10189128)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Electron Paramagnetic Resonance / Electron Paramagnetic Resonance Imaging / Hypertension / Ca Channel Antagonist / Angiotensin II Receptor Antagonist / Oxidative Stress |
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| Research Abstract |
The effect of calcium channel blocker azelnidipine on the redox status of a murine hypertension model was analyzed and imaged using in vivo low frequency electron paramagnetic resonance (EPR).
A murine two kidney-one clip (2K1C) hypertension model was made by a clipping of the right renal artery. The hypertensive mice were treated with low dose azelnidipine (1 mg/ kg/ day), high dose azelnidipine (3 mg /kg /day) or without azelnidipine (HT). An EPR system equipped with a loop-gap resonator and an imaging system was employed. Redox status was evaluated as organ reducing activity measured by means of the decay rate (half-lives) of the spin probe 3-carbamoyl-2, 2, 5, 5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL).
Four weeks after clipping the mice showed hypertension. After the additional two weeks of Azl treatments the Carbamoyl-PROXYL half-lives of the Low and High Azl groups measured in the upper abdominal area were significantly shorter than those of the HT group suggesting improvements in the reducing activity. The blood pressures of the three groups showed no significant differences at this time and there was no correlation between the renal reducing activity and either blood pressure or serum creatinine values. EPR imaging studies revealed that the improvement in abdominal reducing activity was mainly recognized in the kidney but not in the liver.
These results indicate that azelnidipine ameliorates the renal redox status through an improvement in reducing activity independent of blood pressure control.
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