2004 Fiscal Year Final Research Report Summary
Role of reactive oxygen species within the vasomotor center of the brain in hypertension
| Project/Area Number |
15590757
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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 |
Circulatory organs internal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
HIROOKA Yoshitaka Kyushu University, Coronary Care Unit, Kyushu University Hospital, Assistant Professor, 大学病院, 講師 (90284497)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOKAWA Hiroaki Kyushu University, Department of Clinical Medicine, Faculty of Medicine, Associate professor, 大学院・医学研究院, 助教授 (00235681)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Reactive oxygen species / blood pressure / heart rate / sympathetic nervous system / gene / brain / nitric oxide / norepinephrine |
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| Research Abstract |
Oxidative stress increases in hypertension. The aim of this study was to determine whether reactive oxygen species(ROS) are increased in the rostral ventrolateral medulla(RVLM) in the brainstem, where the vasomotor center is located, in stroke-prone spontaneously hypertensive rats(SHRSP), and, if so, to determine whether the increased ROS contribute to neural mechanisms of hypertension in SHRSP. We measured ROS levels in the RVLM of SHRSP and compared them with those in Wistar-Kyoto rats(WKY). Thiobarbituric acid-reactive substances were increased in SHRSP compared with WKY. ROS were also measured by electron spin resonance(ESR) spectroscopy. The ESR signal decay rate in the RVLM of SHRSP was significantly increased compared with that in WKY, and this increase was abolished by dimethylthiourea (a hydroxyl radical scavenger). The increased ESR signal decay was reduced to the same extent in the presence of desferrioxamine, catalase, and Tiron, indicating that hydroxyl radicals are derived from superoxide anions and hydrogen peroxide. In addition, total superoxide dismutase(SOD) activity in the RVLM decreased blood pressure in SHRSP but not in WKY, and MnSOD overexpression in the RVLM of SHRSP decreased blood pressure and inhibited sympathetic nerve activity. These results suggest that superoxide anions in the RVLM, which generate hydroxyl radicals, are increased in SHRSP and contribute to the neural mechanisms of hypertension in SHRSP. We also examined the role of inducible nitric oxide synthase(iNOS) in the RVLM in the control of blood pressure and sympathetic nerve activity. We fond that overexpression of iNOS in the RVLM increases blood pressure via activation of the sympathetic nervous system, which is mediated by an increase in oxidative stress.
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