Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension
Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension
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原发性高血压神经元去甲肾上腺素再摄取缺陷的表型证据
DOI：
10.1161/01.hyp.36.5.824
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
M. Esler
中科院分区：
文献类型：
--
作者：
M. Rumantir;D. Kaye;G. Jennings;M. Vaz;J. Hastings;M. Esler
先前的报道表明，原发性高血压患者神经元去甲肾上腺素（NE）再摄取可能受损，这可能是由于NE转运体功能障碍所致，尽管证据尚无定论。为了进一步验证这一观点，我们应用表型相关的放射性示踪剂方法，输注氚化NE并定量NE代谢物，对34名健康的瘦人（体重指数<27.0 kg/m2）， 19名超重（体重指数>28.0 kg/m2）但其他方面健康的正常受试者，13名未经治疗的瘦人原发性高血压患者和14名肥胖相关高血压患者进行了研究。只有瘦肉高血压患者的NE外溢增加（平均±SD 33.4±20.6，瘦肉正常血压患者为16.1±11.7 ng/min, P <0.05），但这可能是由于心脏交感神经放电率高，NE再摄取错误，或两者兼而有之。3-甲氧基-4-羟基苯乙二醇（NE的神经外代谢物）的动脉血浆浓度仅在瘦型高血压患者中升高（3942±1068 vs 3055±888 pg/mL, P <0.05）。以神经元NE摄取为基础测定的血浆氚化NE通过心脏的分数提取在瘦原发性高血压患者中减少（0.65±0.19比健康受试者的0.81±0.11,P <0.05）。在转运体摄取[3H]NE后，由单胺氧化酶在神经内产生的氚化NE代谢物[3H]二羟基苯乙二醇的心脏释放仅在瘦型高血压患者中减少（健康受试者为992±1435 dpm/min，而健康受试者为4588±3189 dpm/min， P <0.01）。这些研究结果表明，原发性高血压患者神经元对NE的再摄取受损。通过神经信号的放大，这种缺陷可能构成原发性高血压的神经源性变异。在肥胖相关性高血压中，没有表型证据表明NE转运蛋白功能障碍。
Previous reports suggest that neuronal norepinephrine (NE) reuptake may be impaired in essential hypertension, perhaps because of dysfunction of the NE transporter, although the evidence is inconclusive. To further test this proposition, we applied phenotypically relevant radiotracer methodology, infusion of tritiated NE and quantification of NE metabolites, to 34 healthy lean subjects (body mass index <27.0 kg/m2), 19 overweight (body mass index >28.0 kg/m2) but otherwise healthy normotensive subjects, 13 untreated lean patients with essential hypertension, and 14 obesity-related hypertensives. Spillover of NE from the heart was increased in lean hypertensives only (mean±SD 33.4±20.6 versus 16.1±11.7 ng/min in lean normotensives, P <0.05), but this could have resulted from high cardiac sympathetic nerve firing rates, faulty NE reuptake, or both. The arterial plasma concentration of 3-methoxy-4-hydroxylphenylglycol, an extraneuronal metabolite of NE, was elevated in lean hypertensives only (3942±1068 versus 3055±888 pg/mL in healthy subjects, P <0.05). The fractional extraction of plasma tritiated NE in passage through the heart, determined on the basis of neuronal NE uptake, was reduced in lean essential hypertensives (0.65±0.19 versus 0.81±0.11 in healthy subjects, P <0.05). Cardiac release of the tritiated NE metabolite [3H]dihydroxylphenylglycol, produced intraneuronally by monoamine oxidase after uptake of [3H]NE by the transporter, was reduced in lean hypertensives only (992±1435 versus 4588±3189 dpm/min in healthy subjects, P <0.01) These findings suggest that neuronal reuptake of NE is impaired in essential hypertension. Through amplification of the neural signal, such a defect could constitute a neurogenic variant of essential hypertension. In obesity-related hypertension, there was no phenotypic evidence of NE transporter dysfunction.
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影响因子：
4.9
作者：
Rumantir, MS;Vaz, M;Esler, MD
通讯作者：
Esler, MD
影响因子：
--
作者：
MARUNAKA, Y;EATON, DC
通讯作者：
EATON, DC
自发性高血压大鼠尾动脉的高去甲肾上腺素神经支配：对神经效应机制的影响。
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Cassis,LA;Stitzel,RE;Head,RJ
通讯作者：
Head,RJ
清醒大鼠低血压和高渗透压期间中枢神经系统去甲肾上腺素释放。
DOI：
10.1152/ajpregu.1991.260.6.r1071
发表时间：
1991
期刊：
The American journal of physiology
影响因子：
--
作者：
VanHuysse,JW;Bealer,SL
通讯作者：
Bealer,SL