Whole body norepinephrine kinetics in ANG II-salt hypertension in the rat
Whole body norepinephrine kinetics in ANG II-salt hypertension in the rat
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DOI：
10.1152/ajpregu.00819.2007
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发表时间：
2008-04-01
影响因子：
2.8
通讯作者：
Fink, Gregory D.
中科院分区：
文献类型：
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作者：
King, Andrew J.;Novotny, Martin;Fink, Gregory D.
本研究旨在探讨去甲肾上腺素(NE)在慢性血管紧张素Ⅱ-盐性高血压大鼠模型中作为全身交感神经系统(SNS)外流指标的作用。雄性SD大鼠喂饲0.4%(生理盐水)或2%(HS)的氯化钠饲料，用动脉和静脉导管插管。恢复期5天，对照组3天后，皮下注射血管紧张素II 150 ng·kg~(-1)·min~(-1)，连续14天。用放射性同位素稀释法测定对照组第3天、血管紧张素Ⅱ输注第7天和第14天的血浆去甲肾上腺素水平和全身去甲肾上腺素的外溢和清除。为了进行这一分析，在注入示踪剂~3H-NE 90min后，测定动脉血浆中H-3-NE和NE的含量。NS大鼠和HS大鼠的平均动脉压(MAP)在对照组期间相似，而HS大鼠的MAP升高到更高的水平。在对照期间，HS大鼠血浆NE水平呈下降趋势，而NE清除率则呈上升趋势。结果表明，在对照组中，NS和HS大鼠的NE溢出效应相似。在NS大鼠，血浆去甲肾上腺素、去甲肾上腺素外溢和去甲肾上腺素清除量在血管紧张素Ⅱ作用下没有变化。相反，在HS饮食的大鼠，血浆去甲肾上腺素和去甲肾上腺素外溢增加，去甲肾上腺素清除量不变。总之，单独给予HS饮食或在喂养NS的动物中输注Ang II并不影响全局交感神经流出。然而，喂养HS的动物对Ang II的额外高血压反应伴随着SNS的激活。
The purpose of this study was to investigate total body norepinephrine (NE) kinetics as an index of global sympathetic nervous system (SNS) outflow in a rat model of chronic ANG II-salt hypertension. Male Sprague-Dawley rats fed a 0.4% (normal salt, NS) or 2% (HS) NaCl diet were instrumented with arterial and venous catheters. After 5 days of recovery and a 3-day control period, ANG II (150 ng(.)kg(-1.)min(-1)) was given subcutaneously by minipump for 14 days. Plasma NE levels and total body NE spillover and clearance were determined on control day 3 and ANG II infusion days 7 and 14 using radioisotope dilution principles. To perform this analysis, H-3-NE and NE were measured in arterial plasma after a 90-min infusion of tracer amounts of 3H-NE. Mean arterial pressure (MAP) was similar during the control period in NS and HS rats; however, MAP increased to a higher level in HS rats. During the control period, plasma NE tended to be lower in rats on HS, whereas NE clearance tended to be higher in HS rats. As a result NE spillover was similar in NS and HS rats during the control period. In NS rats, plasma NE, NE spillover, and NE clearance were unchanged by ANG II. In contrast, in rats on the HS diet, plasma NE and NE spillover increased during ANG II infusion, whereas NE clearance was unchanged. In conclusion, a HS diet alone or ANG II infusion in animals fed NS do not affect global sympathetic outflow. However, the additional hypertensive response to ANG II in animals fed HS is accompanied by SNS activation.