Lambert G W, Eisenhofer G, Jennings G L, Esler M D
Human Autonomic Function Laboratory, Baker Medical Research Institute, Prahran Vic, Australia.
Life Sci. 1993;53(1):63-75. doi: 10.1016/0024-3205(93)90612-7.
Peripheral plasma levels of homovanillic acid (HVA), the deaminated and o-methylated metabolite of dopamine, are often used as an indicator of central nervous system dopaminergic activity. Using percutaneously placed catheters, we studied the regional inputs into the plasma HVA pool in 60 healthy volunteers. Veno-arterial differences and organ plasma flows were used to quantify the relative amounts of HVA contributed by various sites into the peripheral circulation. Positive arterio-venous HVA gradients were found in the pulmonary, hepatosplanchnic, skeletal muscle and jugular vessels of the normal volunteers. No HVA increment was found in the coronary sinus. The renal circulation was determined to be the principal site of HVA clearance, extracting 27 nmol/min. The regional contributions of HVA were as follows: lungs 21 nmol/min, hepatosplanchnic organs 3 nmol/min, skeletal muscle 3 nmol/min and the brain 4 nmol/min. The pattern of regional HVA production contrasted with that of the deaminated dopamine metabolite, dihydroxyphenylacetic acid, for which the heart was the principal site of production identified. Sixteen patients with chronic congestive heart failure (CHF) and 6 patients with pure autonomic failure (PAF) were also studied to investigate possible effects of sympathetic nervous system overactivity and underactivity on peripheral HVA production and plasma HVA concentration. The resting arterial plasma HVA concentration in CHF was increased approximately 3-fold. Unexpectedly, this was attributable to reduced HVA plasma clearance, not increased HVA production. Total HVA production in PAF was diminished by 40%. PAF patients had normal resting arterial HVA levels, this being accounted for by a 57% fall in the renal plasma clearance of HVA. Acute sympathetic nervous system activation in response to bicycle riding was accompanied by a 34% increase in the arterial concentration of HVA. It can be concluded that HVA is produced at a number of sites throughout the body not renowned for their dopaminergic innervation. Regional HVA production is associated, in part, with the metabolism of precursor dopamine in sympathetic nerves and at a rate which appears to be influenced by sympathetic nervous activity. To obtain an accurate indication of central dopaminergic activity the confounding influences of HVA plasma clearance and peripheral HVA production must be excluded.
高香草酸（HVA）是多巴胺的脱氨基和邻甲基化代谢产物，其外周血浆水平常被用作中枢神经系统多巴胺能活性的指标。我们使用经皮放置的导管，对60名健康志愿者血浆HVA池的区域输入进行了研究。利用静脉 - 动脉差异和器官血浆流量来量化不同部位对周围循环中HVA贡献的相对量。在正常志愿者的肺、肝内脏、骨骼肌和颈静脉中发现了正的动静脉HVA梯度。在冠状窦中未发现HVA增加。确定肾循环是HVA清除的主要部位，每分钟清除27纳摩尔。HVA的区域贡献如下：肺每分钟21纳摩尔，肝内脏器官每分钟3纳摩尔，骨骼肌每分钟3纳摩尔，脑每分钟4纳摩尔。区域HVA产生的模式与脱氨基多巴胺代谢产物二羟基苯乙酸不同，后者确定心脏是主要产生部位。还对16例慢性充血性心力衰竭（CHF）患者和6例纯自主神经功能衰竭（PAF）患者进行了研究，以探讨交感神经系统活动亢进和减退对周围HVA产生和血浆HVA浓度的可能影响。CHF患者静息动脉血浆HVA浓度增加约3倍。出乎意料的是，这是由于HVA血浆清除率降低，而非HVA产生增加。PAF患者的总HVA产生减少了40%。PAF患者静息动脉HVA水平正常，这是由于HVA的肾血浆清除率下降了57%。因骑自行车导致的急性交感神经系统激活伴随着动脉HVA浓度增加34%。可以得出结论，HVA在全身多个并非以多巴胺能神经支配而闻名的部位产生。区域HVA产生部分与交感神经中前体多巴胺的代谢有关，其速率似乎受交感神经活动影响。为准确指示中枢多巴胺能活性，必须排除HVA血浆清除和周围HVA产生的混杂影响。
