Lambert G W, Ferrier C, Kaye D M, Kalff V, Kelly M J, Cox H S, Turner A G, Jennings G L, Esler M D
Human Autonomic Function Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
Blood Press. 1994 Mar;3(1-2):55-66. doi: 10.3109/08037059409101522.
In this study we aimed to elucidate the role of central noradrenergic, dopaminergic, adrenergic and serotonergic neuronal systems in the development of essential hypertension. Fifteen untreated essential hypertensive subjects (aged 44 +/- 3 years) and 32 healthy volunteers (aged 38 +/- 3 years) participated in this study. By combining direct blood sampling techniques with cerebral blood flow scans we were able to differentiate between cortical and subcortical venous drainage of the brain. Veno-arterial MHPG, HVA and 5-HIAA plasma concentration gradients combined with internal jugular vein plasma flows were used, according to the Fick Principle, to derive metabolite spillovers which in turn were used as indicators of central noradrenergic, dopaminergic and serotonergic neuronal activity, respectively. These amine systems, in both the brainstem and forebrain, have been implicated in the regulation of sympathetic outflow and blood pressure. Total body noradrenaline spillover to plasma was concurrently measured to assess the relationship between central monoamine turnover and sympathetic activity. Compared to their healthy counterparts the hypertensive subjects had an elevated release of MHPG from subcortical brain regions (1.4 +/- 0.3 v 0.5 +/- 0.2 nmol/min, p < 0.05). An inverse relationship between blood pressure and subcortical HVA overflow existed, with the HVA overflow being significantly lower in the hypertensives (0.5 +/- 0.2 v 2.1 +/- 0.5 nmol/min, p < 0.05). Subcortical 5-HUAA overflow did not differ between the two groups, and adrenaline spillover from the brain was not detected in either group. Subcortical MHPG overflow was significantly correlated with total body NA spillover to plasma (p < 0.05). These results indicate that reciprocal aberrations in subcortical noradrenaline and dopamine turnover exist in essential hypertension. Although the physiological significance of this remains to be unequivocally elucidated we postulate that elevated subcortical noradrenergic activity, presumably in the forebrain where noradrenergic neurons are pressor, may cause sympathoexcitation and play a role in the development of essential hypertension.
在本研究中，我们旨在阐明中枢去甲肾上腺素能、多巴胺能、肾上腺素能和5-羟色胺能神经元系统在原发性高血压发生发展中的作用。15名未经治疗的原发性高血压患者（年龄44±3岁）和32名健康志愿者（年龄38±3岁）参与了本研究。通过将直接采血技术与脑血流扫描相结合，我们能够区分大脑皮质和皮质下的静脉引流。根据菲克原理，使用静脉-动脉间3-甲氧基-4-羟基苯乙二醇（MHPG）、高香草酸（HVA）和5-羟吲哚乙酸（5-HIAA）血浆浓度梯度结合颈内静脉血浆流量，得出代谢物溢出量，进而分别用作中枢去甲肾上腺素能、多巴胺能和5-羟色胺能神经元活动的指标。脑干和前脑的这些胺能系统均与交感神经传出和血压调节有关。同时测量全身去甲肾上腺素向血浆的溢出量，以评估中枢单胺周转率与交感神经活动之间的关系。与健康对照者相比，高血压患者皮质下脑区的MHPG释放增加（1.4±0.3对0.5±0.2 nmol/分钟，p<0.05）。血压与皮质下HVA溢出量之间存在负相关关系，高血压患者的HVA溢出量显著较低（0.5±0.2对2.1±0.5 nmol/分钟，p<0.05）。两组间皮质下5-HUAA溢出量无差异，且两组均未检测到脑内肾上腺素溢出。皮质下MHPG溢出量与全身去甲肾上腺素向血浆的溢出量显著相关（p<0.05）。这些结果表明，原发性高血压患者存在皮质下去甲肾上腺素和多巴胺周转率的相互异常。尽管其生理意义仍有待明确阐明，但我们推测皮质下去甲肾上腺素能活性升高，可能在前脑（去甲肾上腺素能神经元具有升压作用），可能导致交感神经兴奋，并在原发性高血压的发生发展中起作用。
