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Mechanisms responsible for the attenuating effects of estrogen on cardiovascular responses to psychological stress in the central nervous system and the peripheral vessels

雌激素减弱中枢神经系统和外周血管对心理应激的心血管反应作用的机制

基本信息

批准号：
17590202
负责人：
MORIMOTO Keiko
金额：
$ 2.3万
依托单位：
Nara Women's University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

(1) Sex difference in norepinephrine surge in response to psychological stress through nitric oxide in ratsA mild psychological stress induced by a cage-switch evoked a norepinephrine surge in the male, but not in the female rats. There was a sex difference in the norepinephrine surge in response to psychological stress through nitric oxide (NO), in association with pressor response.(2) Effects of estrogen on plasma catecholamine, NO metabolites (NOx) and 4-hydroxy-2-nonena1 during cage-switch stressEstrogen replacement tended to suppress plasma norepinephrine elevation induced by the stress in ovariectomized rat. Additionally, the NO synthase (NOS) inhibitor decreased this effect of estrogen. By Western blotting analysis, estrogen replacement enhanced basal endothelial NOS expression in mesenteries. Furthermore, estrogen replacement attenuated a basal level of plasma 4-hydroxy-2-nonenal, a marker for oxidative stress, and tended to enhance plasma NOx level.Our results suggest that est … More rogen attenuates the stress-induced pressor response by suppressing oxidative stress and enhancing NO bioavailability(3) Effects of estrogen replacement on neuronal activation induced by cage-switch stress in ovariectomized rat brainThe stress-induced elevations in c-Fos expressions, a marker for neuronal activation, were detected in the following brain areas : lateral septal nucleus, paraventricular hypothalamic nucleus (PVN), dorsomedial hypothalamic nucleus (DMD), arcuate hypothalamic nucleus, paraventricular thalamic nucleus, and locus coeruleus (LC). Estrogen replacement suppressed stress-induced c-Fos expressions in PVN, DMD and LC. In addition, estrogen replacement enhanced the activation of NO-producing neurons in PVN. These findings suggest that estrogen replacement attenuates neuronal activation in these brain areas, at least partly by NO.These results suggest that estrogen replacement suppresses cardiovascular responses to psychological stress at least partly through its anti-oxidative effect on the periphery and through its inhibitory effect on neuronal activation in the brain of ovariectomized rats. Less

(1)心理应激时大鼠一氧化氮介导的去甲肾上腺素峰的性别差异用转笼法诱导的轻度心理应激，在雄性大鼠中引起去甲肾上腺素峰，但在雌性大鼠中没有。通过一氧化氮（NO）对心理应激反应的去甲肾上腺素激增存在性别差异，与升压反应相关。(2)雌激素对转换笼应激大鼠血浆中儿茶酚胺、NO代谢产物（NOx）和4-羟基-2-壬烯醛的影响雌激素替代治疗有抑制应激引起的去甲肾上腺素升高的趋势。此外，一氧化氮合酶（NOS）抑制剂降低了雌激素的这种作用。Western blotting分析显示，雌激素替代增强了肠系膜基底内皮NOS的表达。此外，雌激素替代降低了血浆4-羟基-2-壬烯醛（氧化应激的标志物）的基础水平，并倾向于提高血浆NOx水平。 ...更多信息氮通过抑制氧化应激和提高NO生物利用度来减弱应激诱导的升压反应（3）雌激素替代对卵巢切除大鼠脑中由笼子转换应激诱导的神经元活化的影响在以下脑区域中检测到应激诱导的c-Fos表达（神经元活化的标志物）的升高：外侧隔核、下丘脑室旁核（PVN）、下丘脑背内侧核（DMD）、下丘脑弓状核、丘脑室旁核和蓝斑（LC）。雌激素替代抑制应激诱导的c-Fos在PVN、DMD和LC中的表达。此外，雌激素替代可增强PVN内NO产生神经元的激活。这些研究结果表明，雌激素替代减弱在这些脑区的神经元激活，至少部分由NO。这些结果表明，雌激素替代抑制心血管反应的心理压力至少部分通过其抗氧化作用的外周和通过其抑制作用，在大脑中的卵巢切除大鼠的神经元激活。少