Norepinephrine Kinetics in Essential Hypertension
Norepinephrine Kinetics in Essential Hypertension
复制标题
原发性高血压中的去甲肾上腺素动力学
作者：
M. Esler;G. Jackman;A. Bobik;A. Kelleher;H. Skews;G. Jennings;P. Korner
为了评估原发性高血压患者交感神经系统的功能，我们测定了交感神经递质去甲肾上腺素释放到血浆和从血浆中清除的速率。在正常受试者中，输注至稳态后，氚化/-去甲肾上腺素从血浆中的消失是双指数的，其中$$ = 2.0 ± 0.4分钟（平均值±标准差）和$$ = 33 ± 15分钟。快速去除的组成部分似乎代表神经元摄取去甲肾上腺素：$$延长神经元去甲肾上腺素摄取的选择性抑制剂，地昔帕明，它没有改变的神经元摄取阻滞剂，皮质醇，它延长了周围交感神经功能障碍（特发性自主神经功能不全）的患者。在37名高血压患者中，有8名患者的tbe $> 2.8分钟（范围3.3-6.0分钟），比任何正常受试者都长;这似乎是存在神经元去甲肾上腺素摄取缺陷的假定证据。在这些患者中，去甲肾上腺素溢出到血浆中的速率，释放后逃逸摄取的递质的速率为0.73 ± 0.39 ng/m2/min（43 ± 23 nmol/m2/min），高于正常人的0.36 ± 0.14 ng/m2/min（2.1 ± 0.8 nmol/m2/min）（P < 0.01）。由于肾上腺素能受体暴露于局部高浓度的去甲肾上腺素，神经元摄取去甲肾上腺素的缺陷可能在某些原发性高血压患者血压升高的起源中起重要作用。
SUMMARY To assess sympathetic nervous system function in essential hypertension, we measured tbe rates of release to and removal from plasma of the sympathetic neurorransmltter, norepinephrine. In normal subjects, disappearance of tritiated /-norepinephrlne from plasma, after infusion to steady state, was biexponential, with $$ = 2.0 ± 0.4 minutes (mean ± standard deviation) and $$ = 33 ± 15 minutes. Tbe rapid component of removal seemed to represent neuronal uptake of norepinephrine: the $$ was lengthened by the selective inhibitor of neuronal norepinephrine uptake, desipramine; it was not changed by the extraneuronal uptake blocker, cortlsol; and it was prolonged in patients with peripheral sympathetic nerve dysfunction (idiopathic autonoroic insufficiency). In eight of 37 hypertensive patients, tbe $$ was > 2.8 minutes (range, 3.3-6.0 min), longer than in any normal subject; this appears to be presumptive evidence of the existence of defective neuronal norepinephrine uptake. In these patients tbe rate of spillover of norepinephrine to plasma, of transmitter escaping uptake after release, was 0.73 ± 0.39 Mg/m2/min (43 ± 23 ninoles/m2/min), higher than in normal subjects, 036 ± 0.14 ng/m2/mia (2.1 ± 0.8 nmoles/m2/min) (p < 0.01). A defect in neuronal uptake of norepinephrine, by exposing adrenergic receptors to high local norepinephrine concentration, may be important in the parhogenesis of blood pressure elevation in some patients with essential hypertension.