| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Reactive oxygen species in the brain increase sympathetic nervous system activity. This mechanism contributes to neural mechanism(s) of hypertension. The nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla (RVLM) are key sites in the brain stem for determining the basal sympathetic nervous system activity and baroreflex functon. Therefore, these areas are so called the vasomotor center. NAD(P)H oxidase is a major source of reactive oxygen species and its activation is mediated by small G protein Racl. However, the role of Racl/NAD(P)H oxidase-derived reactive oxygen species in the brain stem of hypertension is not known. Therefore, the aim of the present study was to determine whether inhibition of Racl in the brain stem of stroke-prone spontaneously hypertensive rats (SHRSP) decreases reactive oxygen species generation, thereby reducing blood pressure in this model. We transfected dominant-negative Racl into the NTS and observed blood pressure using a radio-telemetr
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y in conscious SHRSP and normotensive Wistar-Kyoto rats (WKY). Racl activity in the NTS was greater in SHRSP than in WKY. Transfection of dominant-negative Racl into the NTS decreased blood pressure, heart rate, and urinary norepinephrine excretion in SHRSHP, but not in WKY. Inhibition of Racl also attenuated NAD(P)H oxidase activity in the NTS and reactive oxygen species generation. Overexpression of Cu/Zn-SOD in the NTS also reduced blood pressure, heart rate, and urinary norepinephrine excretion in SHRSP, suggesting that scavenging reactive oxygen species inhibits sympathetic nervous system activity thereby reducing blood pressure. These results indicate that Racl-derived reactive oxygen species in the brain stem contribute to neural mechanism(s) of hypertension of SHRSP.
We also demonstrated another small G protein Rho in the brain stem plays an important role in neural control of circulation. In addition, some antihypertensive drugs might reduce reactive oxygen species in the brain. Less
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