| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Voltage dependent potassium currents in endothelial cells were decreased in hypertensive model rats such as SHR and SHR-SP. We previously reported that this alteration was partially due to the decreased expression of Kv 1.5 channel protein. We also observed that antihypertensive treatment on hypertensive rats restored this alteration. We thus hypothesize that renin-angiotensin system plays an important role on the control of potassium channel activities. In the present study, we observed that potassium currents were decreased in mesenteric smooth muscle cells from SHR, as compared to WKY. mRNA expression of Kv2.1 was decreased in SHR, but that of Kv1.5 and Kv1.2 remained the same as compared to WKY. An extracellular oxidative stress, that was produced by bath application of xanthin and xanthin oxidase, did not affect, but an intracellular oxidative stress, that was produced by intracellular application of NADH and NADPH via recording pipette, decreased potassium currents. In addition, intracellular oxidative stress of single cells as measured with H2DCDA was enhanced in SHR than in WKY. Finally, mRNA expression of component of NAD(P)H oxidase such as NOX4, NOX1, and p22 was enhanced in SHR. These results suggest that decreased expression of potassium channels, and enhanced production of oxidative stress may decrease the potassium currents in SHR.
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